Pub Date : 2023-02-23DOI: 10.3389/fviro.2023.1066147
Kevin Surya, Jacob D. Gardner, C. Organ
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) evolved slowly over the first year of the Coronavirus Disease 19 (COVID-19) pandemic with differential mutation rates across lineages. Here, we explore how this variation arose. Whether evolutionary change accumulated gradually within lineages or during viral lineage branching is unclear. Using phylogenetic regression models, we show that ~13% of SARS-CoV-2 genomic divergence up to May 2020 is attributable to lineage branching events (punctuated evolution). The net number of branching events along lineages predicts ~5% of the deviation from the strict molecular clock. We did not detect punctuated evolution in SARS-CoV-1, possibly due to the small sample size, and in sarbecovirus broadly, likely due to a different evolutionary process altogether. Punctuation in SARS-CoV-2 is probably neutral because most mutations were not positively selected and because the strength of the punctuational effect remained constant over time, at least until May 2020, and across continents. However, the small punctuational contribution to SARS-CoV-2 diversity is consistent with the founder effect arising from narrow transmission bottlenecks. Therefore, punctuation in SARS-CoV-2 may represent the macroevolutionary consequence (rate variation) of a microevolutionary process (transmission bottleneck).
{"title":"Detecting punctuated evolution in SARS-CoV-2 over the first year of the pandemic","authors":"Kevin Surya, Jacob D. Gardner, C. Organ","doi":"10.3389/fviro.2023.1066147","DOIUrl":"https://doi.org/10.3389/fviro.2023.1066147","url":null,"abstract":"The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) evolved slowly over the first year of the Coronavirus Disease 19 (COVID-19) pandemic with differential mutation rates across lineages. Here, we explore how this variation arose. Whether evolutionary change accumulated gradually within lineages or during viral lineage branching is unclear. Using phylogenetic regression models, we show that ~13% of SARS-CoV-2 genomic divergence up to May 2020 is attributable to lineage branching events (punctuated evolution). The net number of branching events along lineages predicts ~5% of the deviation from the strict molecular clock. We did not detect punctuated evolution in SARS-CoV-1, possibly due to the small sample size, and in sarbecovirus broadly, likely due to a different evolutionary process altogether. Punctuation in SARS-CoV-2 is probably neutral because most mutations were not positively selected and because the strength of the punctuational effect remained constant over time, at least until May 2020, and across continents. However, the small punctuational contribution to SARS-CoV-2 diversity is consistent with the founder effect arising from narrow transmission bottlenecks. Therefore, punctuation in SARS-CoV-2 may represent the macroevolutionary consequence (rate variation) of a microevolutionary process (transmission bottleneck).","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45571586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-20DOI: 10.3389/fviro.2023.1055487
Makayla Cook, T. Hensley-McBain, Andrea Grindeland
Animal models are essential tools for investigating and understanding complex prion diseases like chronic wasting disease (CWD), an infectious prion disease of cervids (elk, deer, moose, and reindeer). Over the past several decades, numerous mouse models have been generated to aid in the advancement of CWD knowledge and comprehension. These models have facilitated the investigation of pathogenesis, transmission, and potential therapies for CWD. Findings have impacted CWD management and disease outcomes, though much remains unknown, and a cure has yet to be discovered. Studying wildlife for CWD effects is singularly difficult due to the long incubation time, subtle clinical signs at early stages, lack of convenient in-the-field live testing methods, and lack of reproducibility of a controlled laboratory setting. Mouse models in many cases is the first step to understanding the mechanisms of disease in a shortened time frame. Here, we provide a comprehensive review of studies with mouse models in CWD research. We begin by reviewing studies that examined the use of mouse models for bioassays for tissues, bodily fluids, and excreta that spread disease, then address routes of infectivity and infectious load. Next, we delve into studies of genetic factors that influence protein structure. We then move on to immune factors, possible transmission through environmental contamination, and species barriers and differing prion strains. We conclude with studies that make use of cervidized mouse models in the search for therapies for CWD.
{"title":"Mouse models of chronic wasting disease: A review","authors":"Makayla Cook, T. Hensley-McBain, Andrea Grindeland","doi":"10.3389/fviro.2023.1055487","DOIUrl":"https://doi.org/10.3389/fviro.2023.1055487","url":null,"abstract":"Animal models are essential tools for investigating and understanding complex prion diseases like chronic wasting disease (CWD), an infectious prion disease of cervids (elk, deer, moose, and reindeer). Over the past several decades, numerous mouse models have been generated to aid in the advancement of CWD knowledge and comprehension. These models have facilitated the investigation of pathogenesis, transmission, and potential therapies for CWD. Findings have impacted CWD management and disease outcomes, though much remains unknown, and a cure has yet to be discovered. Studying wildlife for CWD effects is singularly difficult due to the long incubation time, subtle clinical signs at early stages, lack of convenient in-the-field live testing methods, and lack of reproducibility of a controlled laboratory setting. Mouse models in many cases is the first step to understanding the mechanisms of disease in a shortened time frame. Here, we provide a comprehensive review of studies with mouse models in CWD research. We begin by reviewing studies that examined the use of mouse models for bioassays for tissues, bodily fluids, and excreta that spread disease, then address routes of infectivity and infectious load. Next, we delve into studies of genetic factors that influence protein structure. We then move on to immune factors, possible transmission through environmental contamination, and species barriers and differing prion strains. We conclude with studies that make use of cervidized mouse models in the search for therapies for CWD.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49434459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-14DOI: 10.3389/fviro.2023.1042724
D. Rajão, G. C. Zanella, Meghan Wymore Brand, Shehroze Khan, Michael E. Miller, L. Ferreri, C. Cáceres, Stivalis Cadernas-Garcia, Carine K. Souza, Tavis K. Anderson, P. Gauger, Amy L. Vincent Baker, D. Pérez
Introduction The rapid evolution of influenza A viruses (FLUAV) complicates disease control for animal and public health. Although vaccination is an effective way to control influenza, available vaccines for use in swine result in limited protection against the antigenically distinct FLUAV that currently co-circulate in pigs. Vaccines administered parenterally usually stimulate IgG antibodies but not strong mucosal IgA or cell-mediated responses, which are typically more cross-reactive. Methods We developed a live attenuated influenza virus (LAIV) vaccine containing IgA-inducing protein (IGIP) as a molecular marker and immunomodulator. This Flu-IGIP vaccine was tested in a bivalent formulation (H1N1 and H3N2) against challenge with antigenically drifted viruses in pigs. Pigs were vaccinated intranasally with either a bivalent Flu-IGIP or a bivalent Flu-att (control without IGIP) and boosted two weeks later. Three weeks post boost, pigs were challenged with antigenically drifted H1N1 or H3N2 virus. Results Vaccinated pigs had increased numbers of influenza-specific IgA-secreting cells in PBMC two weeks post boost and higher numbers of total and influenza-specific IgA-secreting cells in bronchoalveolar lavage fluid (BALF) 5 days post inoculation (dpi) compared to naïve pigs. Pigs vaccinated with both Flu-IGIP and Flu-att shed significantly less virus after H1N1 or H3N2 challenge compared to non-vaccinated pigs. Vaccination with Flu-att reduced respiratory transmission, while Flu-IGIP fully blocked transmission regardless of challenge virus. Both Flu-IGIP and Flu-att vaccines reduced virus replication in the lungs and lung lesions after inoculation with either virus. IgG and IgA levels in BALF and nasal wash of vaccinated pigs were boosted after inoculation as soon as 5 dpi and remained high at 14 dpi. Conclusion Our results indicate that Flu-IGIP leads to protection from clinical signs, replication and shedding after antigenically drifted influenza virus infection.
{"title":"Live attenuated influenza A virus vaccine expressing an IgA-inducing protein protects pigs against replication and transmission","authors":"D. Rajão, G. C. Zanella, Meghan Wymore Brand, Shehroze Khan, Michael E. Miller, L. Ferreri, C. Cáceres, Stivalis Cadernas-Garcia, Carine K. Souza, Tavis K. Anderson, P. Gauger, Amy L. Vincent Baker, D. Pérez","doi":"10.3389/fviro.2023.1042724","DOIUrl":"https://doi.org/10.3389/fviro.2023.1042724","url":null,"abstract":"Introduction The rapid evolution of influenza A viruses (FLUAV) complicates disease control for animal and public health. Although vaccination is an effective way to control influenza, available vaccines for use in swine result in limited protection against the antigenically distinct FLUAV that currently co-circulate in pigs. Vaccines administered parenterally usually stimulate IgG antibodies but not strong mucosal IgA or cell-mediated responses, which are typically more cross-reactive. Methods We developed a live attenuated influenza virus (LAIV) vaccine containing IgA-inducing protein (IGIP) as a molecular marker and immunomodulator. This Flu-IGIP vaccine was tested in a bivalent formulation (H1N1 and H3N2) against challenge with antigenically drifted viruses in pigs. Pigs were vaccinated intranasally with either a bivalent Flu-IGIP or a bivalent Flu-att (control without IGIP) and boosted two weeks later. Three weeks post boost, pigs were challenged with antigenically drifted H1N1 or H3N2 virus. Results Vaccinated pigs had increased numbers of influenza-specific IgA-secreting cells in PBMC two weeks post boost and higher numbers of total and influenza-specific IgA-secreting cells in bronchoalveolar lavage fluid (BALF) 5 days post inoculation (dpi) compared to naïve pigs. Pigs vaccinated with both Flu-IGIP and Flu-att shed significantly less virus after H1N1 or H3N2 challenge compared to non-vaccinated pigs. Vaccination with Flu-att reduced respiratory transmission, while Flu-IGIP fully blocked transmission regardless of challenge virus. Both Flu-IGIP and Flu-att vaccines reduced virus replication in the lungs and lung lesions after inoculation with either virus. IgG and IgA levels in BALF and nasal wash of vaccinated pigs were boosted after inoculation as soon as 5 dpi and remained high at 14 dpi. Conclusion Our results indicate that Flu-IGIP leads to protection from clinical signs, replication and shedding after antigenically drifted influenza virus infection.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42372081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-08DOI: 10.3389/fviro.2023.1125448
L. C. Lesmes-Rodríguez, Humaira Lambarey, Abeen Chetram, C. Riou, R. Wilkinson, Wendy Joyimbana, L. Jennings, C. Orrell, Dumar A. Jaramillo-Hernández, Georgia Schäfer
Background Globally, the most significant risk factors for adverse COVID-19 outcome are increasing age and cardiometabolic comorbidities. However, underlying coinfections may modulate COVID-19 morbidity and mortality, particularly in regions with high prevalence of infectious diseases. Methods We retrospectively analyzed serum samples for IgG antibodies against the common circulating coronaviruses HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 from non-hospitalized and hospitalized confirmed COVID-19 patients recruited during the first (June-August 2020) and second (October 2020-June 2021) COVID-19 wave in Cape Town, South Africa. Patients were grouped according to COVID-19 disease severity: Group 1: previously SARS-CoV-2 infected with positive serology and no symptoms (n=94); Group 2: acutely SARS-CoV-2 infected, hospitalized for COVID-19 and severe symptoms (n=92). Results The overall anti-HCoV IgG seroprevalence in the entire patient cohort was 60.8% (95% CI: 53.7 – 67.8), with 37.1% HCoV-NL63 (95% CI: 30 – 44), 30.6% HCoV-229E (95% CI: 24 – 37.3), 22.6% HCoV-HKU1 (95% CI: 16.6 – 28.6), and 21.0% HCoV-OC43 (95% CI: 15.1 – 26.8). We observed a significantly higher overall HCoV presence (72.3% versus 48.9%) and coinfection frequency (43.6% versus 19.6%) in group 1 compared to group 2 patients with significantly higher presentation of HCoV-NL63 (67.0% versus 6.6%) and HCoV-HKU1 (31.1% versus 14.1%). However, only antibody titers for HCoV-NL63 were significantly higher in group 1 compared to group 2 patients (p< 0.0001, 1.90 [95% CI: 0.62 – 2.45] versus 1.32 [95% CI: 0.30 – 2.01]) which was independent of the participants’ HIV status. Logistic regression analysis revealed significantly protective effects by previous exposure to HCoV-NL63 [p< 0.001, adjusted OR = 0.0176 (95% CI: 0.0039 – 0.0786)], while previous HCoV-229E exposure was associated with increased COVID-19 severity [p = 0.0051, adjusted OR = 7.3239 (95% CI: 1.8195–29.4800)]. Conclusion We conclude that previous exposure to multiple common coronaviruses, and particularly HCoV-NL63, might protect against severe COVID-19, while no previous HCoV exposure or single infection with HCoV-229E might enhance the risk for severe COVID-19. To our knowledge, this is the first report on HCoV seroprevalence in South Africa and its possible association with cross-protection against COVID-19 severity.
{"title":"Previous exposure to common coronavirus HCoV-NL63 is associated with reduced COVID-19 severity in patients from Cape Town, South Africa","authors":"L. C. Lesmes-Rodríguez, Humaira Lambarey, Abeen Chetram, C. Riou, R. Wilkinson, Wendy Joyimbana, L. Jennings, C. Orrell, Dumar A. Jaramillo-Hernández, Georgia Schäfer","doi":"10.3389/fviro.2023.1125448","DOIUrl":"https://doi.org/10.3389/fviro.2023.1125448","url":null,"abstract":"Background Globally, the most significant risk factors for adverse COVID-19 outcome are increasing age and cardiometabolic comorbidities. However, underlying coinfections may modulate COVID-19 morbidity and mortality, particularly in regions with high prevalence of infectious diseases. Methods We retrospectively analyzed serum samples for IgG antibodies against the common circulating coronaviruses HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 from non-hospitalized and hospitalized confirmed COVID-19 patients recruited during the first (June-August 2020) and second (October 2020-June 2021) COVID-19 wave in Cape Town, South Africa. Patients were grouped according to COVID-19 disease severity: Group 1: previously SARS-CoV-2 infected with positive serology and no symptoms (n=94); Group 2: acutely SARS-CoV-2 infected, hospitalized for COVID-19 and severe symptoms (n=92). Results The overall anti-HCoV IgG seroprevalence in the entire patient cohort was 60.8% (95% CI: 53.7 – 67.8), with 37.1% HCoV-NL63 (95% CI: 30 – 44), 30.6% HCoV-229E (95% CI: 24 – 37.3), 22.6% HCoV-HKU1 (95% CI: 16.6 – 28.6), and 21.0% HCoV-OC43 (95% CI: 15.1 – 26.8). We observed a significantly higher overall HCoV presence (72.3% versus 48.9%) and coinfection frequency (43.6% versus 19.6%) in group 1 compared to group 2 patients with significantly higher presentation of HCoV-NL63 (67.0% versus 6.6%) and HCoV-HKU1 (31.1% versus 14.1%). However, only antibody titers for HCoV-NL63 were significantly higher in group 1 compared to group 2 patients (p< 0.0001, 1.90 [95% CI: 0.62 – 2.45] versus 1.32 [95% CI: 0.30 – 2.01]) which was independent of the participants’ HIV status. Logistic regression analysis revealed significantly protective effects by previous exposure to HCoV-NL63 [p< 0.001, adjusted OR = 0.0176 (95% CI: 0.0039 – 0.0786)], while previous HCoV-229E exposure was associated with increased COVID-19 severity [p = 0.0051, adjusted OR = 7.3239 (95% CI: 1.8195–29.4800)]. Conclusion We conclude that previous exposure to multiple common coronaviruses, and particularly HCoV-NL63, might protect against severe COVID-19, while no previous HCoV exposure or single infection with HCoV-229E might enhance the risk for severe COVID-19. To our knowledge, this is the first report on HCoV seroprevalence in South Africa and its possible association with cross-protection against COVID-19 severity.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42426384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-31DOI: 10.3389/fviro.2023.1130102
A. Beukenhorst, J. Frallicciardi, Clarissa M. Koch, J. Klap, Angela M. Phillips, Michael M. Desai, K. Wichapong, G. Nicolaes, W. Koudstaal, G. Alter, J. Goudsmit
{"title":"Corrigendum: The influenza hemagglutinin stem antibody CR9114: Evidence for a narrow evolutionary path towards universal protection","authors":"A. Beukenhorst, J. Frallicciardi, Clarissa M. Koch, J. Klap, Angela M. Phillips, Michael M. Desai, K. Wichapong, G. Nicolaes, W. Koudstaal, G. Alter, J. Goudsmit","doi":"10.3389/fviro.2023.1130102","DOIUrl":"https://doi.org/10.3389/fviro.2023.1130102","url":null,"abstract":"","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91288178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-30DOI: 10.3389/fviro.2022.1009382
C. Diagne, Idrissa Dieng, O. Faye, C. Fall, M. A. Barry, M. Diarra, Oumar Ndiaye, Marie Henriette Dior Ndione, M. Ndiaye, B. Diop, A. Bousso, A. Sall, G. Fall, C. Loucoubar, Y. Bâ, A. Sall, M. Diallo, O. Faye
On 10th September 2018, the Syndromic Sentinel Surveillance network that monitors febrile illnesses in all 14 regions of Senegal detected a peak of fever in the Fatick region. On 13 September 2018, 10 samples were sent to the WHO Collaborating Centre for Arboviruses and Viral Haemorrhagic Fevers at the Institut Pasteur de Dakar (IPD). Laboratory investigations revealed an epidemic of dengue 1 genotype V and dengue 3 genotype III. Fatick neighbors the Holy City of Touba where 3.5 million people from all over the word gather every year for the Grand Magal pilgrimage. This article discusses the impact of mass gatherings and their role in the recent introduction of dengue serotypes in Senegal. Dengue is now endemic in Senegal and across many countries in Africa, highlighting the need for early detection, control measures and prevention of severe dengue cases in highly connected urban settings.
{"title":"Co-circulation of dengue virus serotypes 1 and 3 in the Fatick region of senegal 2018","authors":"C. Diagne, Idrissa Dieng, O. Faye, C. Fall, M. A. Barry, M. Diarra, Oumar Ndiaye, Marie Henriette Dior Ndione, M. Ndiaye, B. Diop, A. Bousso, A. Sall, G. Fall, C. Loucoubar, Y. Bâ, A. Sall, M. Diallo, O. Faye","doi":"10.3389/fviro.2022.1009382","DOIUrl":"https://doi.org/10.3389/fviro.2022.1009382","url":null,"abstract":"On 10th September 2018, the Syndromic Sentinel Surveillance network that monitors febrile illnesses in all 14 regions of Senegal detected a peak of fever in the Fatick region. On 13 September 2018, 10 samples were sent to the WHO Collaborating Centre for Arboviruses and Viral Haemorrhagic Fevers at the Institut Pasteur de Dakar (IPD). Laboratory investigations revealed an epidemic of dengue 1 genotype V and dengue 3 genotype III. Fatick neighbors the Holy City of Touba where 3.5 million people from all over the word gather every year for the Grand Magal pilgrimage. This article discusses the impact of mass gatherings and their role in the recent introduction of dengue serotypes in Senegal. Dengue is now endemic in Senegal and across many countries in Africa, highlighting the need for early detection, control measures and prevention of severe dengue cases in highly connected urban settings.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45721802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-17DOI: 10.3389/fviro.2022.1078953
Tehillah Taonga Chinunga, B. Titanji, A. Chahroudi
The advancement of science has been a collective effort and benefits from a diversity of views and gender representation. However, support for and recognition of women in science is often insufficient. Despite historically being marginalized by the scientific community, research by women has advanced the field of virology, from the discovery of rotavirus and isolation of human immunodeficiency virus (HIV) to a vaccine for polio and the initial description of a virus’ ability to cause cancer. Although women in science, technology, engineering, and mathematics (STEM) fields are continuing to share their diverse wealth of knowledge and innovation, even today many are under-recognized and under-supported in low- and middle-income countries (LMICs). This review will highlight women in virology from LMICs in Africa, Asia, and Latin America where the barriers to scientific education and achievement for women can be far greater than in high income countries. Despite these barriers, the women we profile below have made important contributions to translational virology. We hope this review will contribute to the global expansion of efforts to provide improved access to and retention in scientific careers for women.
{"title":"Breaking barriers: Scientific contributions in virology from women in low- and middle-income countries","authors":"Tehillah Taonga Chinunga, B. Titanji, A. Chahroudi","doi":"10.3389/fviro.2022.1078953","DOIUrl":"https://doi.org/10.3389/fviro.2022.1078953","url":null,"abstract":"The advancement of science has been a collective effort and benefits from a diversity of views and gender representation. However, support for and recognition of women in science is often insufficient. Despite historically being marginalized by the scientific community, research by women has advanced the field of virology, from the discovery of rotavirus and isolation of human immunodeficiency virus (HIV) to a vaccine for polio and the initial description of a virus’ ability to cause cancer. Although women in science, technology, engineering, and mathematics (STEM) fields are continuing to share their diverse wealth of knowledge and innovation, even today many are under-recognized and under-supported in low- and middle-income countries (LMICs). This review will highlight women in virology from LMICs in Africa, Asia, and Latin America where the barriers to scientific education and achievement for women can be far greater than in high income countries. Despite these barriers, the women we profile below have made important contributions to translational virology. We hope this review will contribute to the global expansion of efforts to provide improved access to and retention in scientific careers for women.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46672068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-10DOI: 10.3389/fviro.2022.822153
L. Taramasso, L. Labate, F. Briano, G. Brucci, S. Mora, S. Blanchi, M. Giacomini, M. Bassetti, A. di Biagio
Introduction Despite the high level of efficacy of modern antiretroviral therapy (ART) in reducing HIV viremia and the control of viral replication, some people living with HIV (PLWH) do not recover their CD4+ T cell count. Methods To evaluate the frequency and predictive factors of discordant immune responses, we performed a retrospective cohort study of 324 antiretroviral-naïve PLWH who initiated first-line ART between 2008 and 2018 and maintained HIV RNA < 50 copies/ml during 36 months of follow-up. PLWH were defined as immunological non-responders (INRs) when CD4+ T cell count was < 20% compared with baseline (INR20%), or < 500 cells/mm3 (INR500) or < 200 cells/mm3 (INR200) at 36 months. Results The prevalence of INR20%, INR500, and INR200 was 12.5%, 34.6%, and 1.5%, respectively. After adjustment for possible confounders, CD4 nadir showed a significant association with all INR definitions, with lower values predicting INR500 (aOR 0.98, 95% CI 0.98–0.99, p < 0.001) and INR200 (aOR 0.98, 95% CI 0.95–1.01, p = 0.096). Moreover, a higher baseline CD4/CD8 ratio was inversely related to the probability of being INR500 (OR 0.03, 95% CI 0.01–0.12, p < 0.001) and INR200 (OR 0.002, 95% CI 18–7–67.72, p = 0.255). By contrast, INR20% had a higher CD4 nadir and CD4/CD8 ratio than other INRs, suggesting the identification of an heterogenous population with such definition. Discussion The present study highlights how INR200 has become rare in the contemporary ART era, and about one-third of PLWH meet the criteria for INR500. Overcoming the threshold of 500 CD4/mm3 could be an appropriate definition of immune response, in contrast with the older definitions of INR200 and INR20%. Early diagnosis and rapid treatment initiation, before CD4 counts and the CD4/CD8 ratio begin to decline, are critical for achieving an optimal immune response.
尽管现代抗逆转录病毒疗法(ART)在降低HIV病毒血症和控制病毒复制方面具有很高的疗效，但一些HIV感染者(PLWH)的CD4+ T细胞计数并没有恢复。方法为了评估不协调免疫应答的频率和预测因素，我们对324名antiretroviral-naïve PLWH进行了回顾性队列研究，这些患者在2008年至2018年期间开始一线抗逆转录病毒治疗，并在36个月的随访期间保持HIV RNA < 50拷贝/ml。当CD4+ T细胞计数与基线相比< 20% (INR20%)，或36个月时< 500细胞/mm3 (INR500)或< 200细胞/mm3 (INR200)时，PLWH被定义为免疫无应答(INRs)。结果INR20%、INR500和INR200的患病率分别为12.5%、34.6%和1.5%。在对可能的混杂因素进行调整后，CD4最低点显示出与所有INR定义的显著关联，较低的值预测INR500 (aOR 0.98, 95% CI 0.98 - 0.99, p < 0.001)和INR200 (aOR 0.98, 95% CI 0.95-1.01, p = 0.096)。此外，较高的基线CD4/CD8比值与INR500 (OR 0.03, 95% CI 0.01-0.12, p < 0.001)和INR200 (OR 0.002, 95% CI 18-7-67.72, p = 0.255)的概率呈负相关。相比之下，INR20%的CD4最低点和CD4/CD8比值高于其他inr，表明具有这种定义的异质性人群。本研究强调了INR200在当代ART时代是如何变得罕见的，大约三分之一的PLWH符合INR500的标准。与以前的定义INR200和INR20%相比，超过500 CD4/mm3的阈值可能是免疫反应的适当定义。在CD4计数和CD4/CD8比值开始下降之前，早期诊断和快速治疗是实现最佳免疫反应的关键。
{"title":"CD4+ T lymphocyte recovery in the modern antiretroviral therapy era: Toward a new threshold for defining immunological non-responders","authors":"L. Taramasso, L. Labate, F. Briano, G. Brucci, S. Mora, S. Blanchi, M. Giacomini, M. Bassetti, A. di Biagio","doi":"10.3389/fviro.2022.822153","DOIUrl":"https://doi.org/10.3389/fviro.2022.822153","url":null,"abstract":"Introduction Despite the high level of efficacy of modern antiretroviral therapy (ART) in reducing HIV viremia and the control of viral replication, some people living with HIV (PLWH) do not recover their CD4+ T cell count. Methods To evaluate the frequency and predictive factors of discordant immune responses, we performed a retrospective cohort study of 324 antiretroviral-naïve PLWH who initiated first-line ART between 2008 and 2018 and maintained HIV RNA < 50 copies/ml during 36 months of follow-up. PLWH were defined as immunological non-responders (INRs) when CD4+ T cell count was < 20% compared with baseline (INR20%), or < 500 cells/mm3 (INR500) or < 200 cells/mm3 (INR200) at 36 months. Results The prevalence of INR20%, INR500, and INR200 was 12.5%, 34.6%, and 1.5%, respectively. After adjustment for possible confounders, CD4 nadir showed a significant association with all INR definitions, with lower values predicting INR500 (aOR 0.98, 95% CI 0.98–0.99, p < 0.001) and INR200 (aOR 0.98, 95% CI 0.95–1.01, p = 0.096). Moreover, a higher baseline CD4/CD8 ratio was inversely related to the probability of being INR500 (OR 0.03, 95% CI 0.01–0.12, p < 0.001) and INR200 (OR 0.002, 95% CI 18–7–67.72, p = 0.255). By contrast, INR20% had a higher CD4 nadir and CD4/CD8 ratio than other INRs, suggesting the identification of an heterogenous population with such definition. Discussion The present study highlights how INR200 has become rare in the contemporary ART era, and about one-third of PLWH meet the criteria for INR500. Overcoming the threshold of 500 CD4/mm3 could be an appropriate definition of immune response, in contrast with the older definitions of INR200 and INR20%. Early diagnosis and rapid treatment initiation, before CD4 counts and the CD4/CD8 ratio begin to decline, are critical for achieving an optimal immune response.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42463113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-04DOI: 10.3389/fviro.2022.1064882
Maja Vukovikj, Golubinka Boshevska, Elizabeta Janchevska, Teodora Buzharova, Ardian Preshova, Milica Simova, Aneta Peshnacka, Dragan Kocinski, G. Kuzmanovska, S. Memeti, I. Gjorgoski
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a persistent negative impact on both the public health and the global economy. To comprehend the origin, transmission routes and discover the mutations that alter the virus’s transmissibility and pathogenicity, full-length SARS-CoV-2 genomes have to be molecularly characterized. Focusing on a two-year time frame (2020-2021), we provide an in-depth virologic and epidemiological overview of the SARS-CoV-2 pandemic in the Republic of North Macedonia by assessing the frequency and distribution of the circulating SARS-CoV-2 variants. Using genetic characterization and phylogenetic analysis we shed light on the molecular evolution of the virus as well as test for a possible connection between specific SARS-CoV-2 haplotypes and the severity of the clinical symptoms. Our results show that one fifth (21.51%) of the tested respiratory samples for SARS-CoV-2 were positive. A noticeable trend in the incidence and severity of the COVID-19 infections was observed in the 60+ age group between males and females. Of the total number of positive cases, the highest incidence of SARS-CoV-2 was noticed in 60+ males (4,170.4/100,000), with a statistically significant (0,0001) difference between the two sexes. Additionally, a 1.8x increase in male mortality and consequentially significantly higher number of death cases was observed compared to females of the same age group (0.001). A total of 327 samples were sequenced in the period March 2020 - August 2021, showing the temporal distribution of SARS-CoV-2 variants circulating in North Macedonia. The phylogenetic analysis showed that most of the viral genomes were closely related and clustered in four distinctive lineages, B.1, B.1.1.7, B.1.351 and B.1.617.2. A statistically significant difference was observed in the 2C_1 haplotype (p=0.0013), where 10.5% of the patients were hospitalized due to severe clinical condition. By employing genetic sequencing, coupled with epidemiological investigations, we investigated viral distribution patterns, identified emerging variants and detected vaccine breakthrough infections. The present work is the first molecular study giving a comprehensive overview of the genetic landscape of circulating SARS-CoV-2 viruses in North Macedonia in a period of two years.
{"title":"In-depth genetic characterization of the SARS-CoV-2 pandemic in a two-year frame in North Macedonia using second and third generation sequencing technologies","authors":"Maja Vukovikj, Golubinka Boshevska, Elizabeta Janchevska, Teodora Buzharova, Ardian Preshova, Milica Simova, Aneta Peshnacka, Dragan Kocinski, G. Kuzmanovska, S. Memeti, I. Gjorgoski","doi":"10.3389/fviro.2022.1064882","DOIUrl":"https://doi.org/10.3389/fviro.2022.1064882","url":null,"abstract":"The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a persistent negative impact on both the public health and the global economy. To comprehend the origin, transmission routes and discover the mutations that alter the virus’s transmissibility and pathogenicity, full-length SARS-CoV-2 genomes have to be molecularly characterized. Focusing on a two-year time frame (2020-2021), we provide an in-depth virologic and epidemiological overview of the SARS-CoV-2 pandemic in the Republic of North Macedonia by assessing the frequency and distribution of the circulating SARS-CoV-2 variants. Using genetic characterization and phylogenetic analysis we shed light on the molecular evolution of the virus as well as test for a possible connection between specific SARS-CoV-2 haplotypes and the severity of the clinical symptoms. Our results show that one fifth (21.51%) of the tested respiratory samples for SARS-CoV-2 were positive. A noticeable trend in the incidence and severity of the COVID-19 infections was observed in the 60+ age group between males and females. Of the total number of positive cases, the highest incidence of SARS-CoV-2 was noticed in 60+ males (4,170.4/100,000), with a statistically significant (0,0001) difference between the two sexes. Additionally, a 1.8x increase in male mortality and consequentially significantly higher number of death cases was observed compared to females of the same age group (0.001). A total of 327 samples were sequenced in the period March 2020 - August 2021, showing the temporal distribution of SARS-CoV-2 variants circulating in North Macedonia. The phylogenetic analysis showed that most of the viral genomes were closely related and clustered in four distinctive lineages, B.1, B.1.1.7, B.1.351 and B.1.617.2. A statistically significant difference was observed in the 2C_1 haplotype (p=0.0013), where 10.5% of the patients were hospitalized due to severe clinical condition. By employing genetic sequencing, coupled with epidemiological investigations, we investigated viral distribution patterns, identified emerging variants and detected vaccine breakthrough infections. The present work is the first molecular study giving a comprehensive overview of the genetic landscape of circulating SARS-CoV-2 viruses in North Macedonia in a period of two years.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43036528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-02-28DOI: 10.3389/fviro.2023.1108420
Jennifer Tisoncik-Go, Kathleen M Voss, Thomas B Lewis, Antonio E Muruato, LaRene Kuller, Eric E Finn, Dillon Betancourt, Solomon Wangari, Joel Ahrens, Naoto Iwayama, Richard F Grant, Robert D Murnane, Paul T Edlefsen, Deborah H Fuller, Glen N Barber, Michael Gale, Megan A O'Connor
Zika virus (ZIKV) is a mosquito-borne flavivirus that causes an acute febrile illness. ZIKV can be transmitted between sexual partners and from mother to fetus. Infection is strongly associated with neurologic complications in adults, including Guillain-Barré syndrome and myelitis, and congenital ZIKV infection can result in fetal injury and congenital Zika syndrome (CZS). Development of an effective vaccine is imperative to protect against ZIKV vertical transmission and CZS. Recombinant Vesicular Stomatitis virus (rVSV) is a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. Here, we evaluate an rVSV vaccine expressing the full length pre-membrane (prM) and ZIKV envelope (E) proteins (VSV-ZprME), shown to be immunogenic in murine models of ZIKV infection, for its capacity to induce immune responses in nonhuman primates. Moreover, we assess the efficacy of the rVSVΔM-ZprME vaccine in the protection of pigtail macaques against ZIKV infection. Administration of the rVSVΔM-ZprME vaccine was safe, but it did not induce robust anti-ZIKV T-cell responses, IgM or IgG antibodies, or neutralizing antibodies in most animals. Post ZIKV challenge, animals that received the rVSVΔM control vaccine lacking ZIKV antigen had higher levels of plasma viremia compared to animals that received the rVSVΔM-ZprME vaccine. Anti-ZIKV neutralizing Ab titers were detected in a single animal that received the rVSVΔM-ZprME vaccine that was associated with reduced plasma viremia. The overall suboptimal ZIKV-specific cellular and humoral responses post-immunization indicates the rVSVΔM-ZprME vaccine did not elicit an immune response in this pilot study. However, recall antibody response to the rVSVΔM-ZprME vaccine indicates it may be immunogenic and further developments to the vaccine construct could enhance its potential as a vaccine candidate in a nonhuman primate pre-clinical model.
{"title":"Evaluation of the immunogenicity and efficacy of an rVSV vaccine against Zika virus infection in macaca nemestrina.","authors":"Jennifer Tisoncik-Go, Kathleen M Voss, Thomas B Lewis, Antonio E Muruato, LaRene Kuller, Eric E Finn, Dillon Betancourt, Solomon Wangari, Joel Ahrens, Naoto Iwayama, Richard F Grant, Robert D Murnane, Paul T Edlefsen, Deborah H Fuller, Glen N Barber, Michael Gale, Megan A O'Connor","doi":"10.3389/fviro.2023.1108420","DOIUrl":"10.3389/fviro.2023.1108420","url":null,"abstract":"<p><p>Zika virus (ZIKV) is a mosquito-borne flavivirus that causes an acute febrile illness. ZIKV can be transmitted between sexual partners and from mother to fetus. Infection is strongly associated with neurologic complications in adults, including Guillain-Barré syndrome and myelitis, and congenital ZIKV infection can result in fetal injury and congenital Zika syndrome (CZS). Development of an effective vaccine is imperative to protect against ZIKV vertical transmission and CZS. Recombinant Vesicular Stomatitis virus (rVSV) is a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. Here, we evaluate an rVSV vaccine expressing the full length pre-membrane (prM) and ZIKV envelope (E) proteins (VSV-ZprME), shown to be immunogenic in murine models of ZIKV infection, for its capacity to induce immune responses in nonhuman primates. Moreover, we assess the efficacy of the rVSVΔM-ZprME vaccine in the protection of pigtail macaques against ZIKV infection. Administration of the rVSVΔM-ZprME vaccine was safe, but it did not induce robust anti-ZIKV T-cell responses, IgM or IgG antibodies, or neutralizing antibodies in most animals. Post ZIKV challenge, animals that received the rVSVΔM control vaccine lacking ZIKV antigen had higher levels of plasma viremia compared to animals that received the rVSVΔM-ZprME vaccine. Anti-ZIKV neutralizing Ab titers were detected in a single animal that received the rVSVΔM-ZprME vaccine that was associated with reduced plasma viremia. The overall suboptimal ZIKV-specific cellular and humoral responses post-immunization indicates the rVSVΔM-ZprME vaccine did not elicit an immune response in this pilot study. However, recall antibody response to the rVSVΔM-ZprME vaccine indicates it may be immunogenic and further developments to the vaccine construct could enhance its potential as a vaccine candidate in a nonhuman primate pre-clinical model.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10306241/pdf/nihms-1902797.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9734866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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