Pub Date : 2023-06-27DOI: 10.3389/fviro.2023.1198361
Ana C. Maretti‐Mira, M. Salomon, Angela M. Hsu, C. Matsuba, L. Golden‐Mason
Introduction Despite advancements in hepatitis C virus (HCV) infection treatment, HCV still represents a significant public health burden. Besides progressive hepatic damage, viral persistence has lasting effects on innate and adaptive immune responses. Lack of a complete understanding of the factors driving an effective HCV response contributes to the failure to develop a vaccine for prevention. This study advances the existing knowledge on HCV-specific CD8+ T cells and describes the impact of current or past HCV infection on CD8+ T cells specific for other viruses. Methods We used barcoded-dextramers to identify and sort CD8+ T cells specific for HCV, cytomegalovirus, and influenza, and characterized them using single-cell RNA sequencing technology. Our cohort included chronic (cHCV), spontaneously resolved (rHCV), and subjects undergoing direct-acting antiviral (DAA) therapy. Results We show that HCV-specific CD8+ T cells have cytotoxic features in patients with cHCV, which is progressively reduced with DAA therapy and persists 12 weeks after treatment completion. We also observe a shift in the CD8+ T cell phenotype on DAA treatment, with decreased effector memory and exhausted cell signatures. In rHCV, we also detected a smaller proportion of effector memory cells compared to cHCV. The proportion of CD8+ exhausted T cells in cHCV and rHCV subjects was comparable. Moreover, we also observed that non-HCV virus-specific CD8+ T cells exhibit robust cytotoxic traits during cHCV infection. Discussion Altogether, our findings suggest that cHCV infection promotes cytotoxicity in CD8+ T cells regardless of virus specificity. The immunological changes caused by cHCV infection in CD8+ T cells may contribute to worsening the ongoing hepatic damage caused by HCV infection or exacerbate the immune response to possible co-infections. Our data provide a resource to groups exploring the underlying mechanisms of HCV-specific T cell spontaneous and treatment-induced resolution to inform the development of effective vaccines against HCV infection.
{"title":"Chronic HCV infection promotes cytotoxicity in antigen-specific CD8+ T cells regardless of virus specificity","authors":"Ana C. Maretti‐Mira, M. Salomon, Angela M. Hsu, C. Matsuba, L. Golden‐Mason","doi":"10.3389/fviro.2023.1198361","DOIUrl":"https://doi.org/10.3389/fviro.2023.1198361","url":null,"abstract":"Introduction Despite advancements in hepatitis C virus (HCV) infection treatment, HCV still represents a significant public health burden. Besides progressive hepatic damage, viral persistence has lasting effects on innate and adaptive immune responses. Lack of a complete understanding of the factors driving an effective HCV response contributes to the failure to develop a vaccine for prevention. This study advances the existing knowledge on HCV-specific CD8+ T cells and describes the impact of current or past HCV infection on CD8+ T cells specific for other viruses. Methods We used barcoded-dextramers to identify and sort CD8+ T cells specific for HCV, cytomegalovirus, and influenza, and characterized them using single-cell RNA sequencing technology. Our cohort included chronic (cHCV), spontaneously resolved (rHCV), and subjects undergoing direct-acting antiviral (DAA) therapy. Results We show that HCV-specific CD8+ T cells have cytotoxic features in patients with cHCV, which is progressively reduced with DAA therapy and persists 12 weeks after treatment completion. We also observe a shift in the CD8+ T cell phenotype on DAA treatment, with decreased effector memory and exhausted cell signatures. In rHCV, we also detected a smaller proportion of effector memory cells compared to cHCV. The proportion of CD8+ exhausted T cells in cHCV and rHCV subjects was comparable. Moreover, we also observed that non-HCV virus-specific CD8+ T cells exhibit robust cytotoxic traits during cHCV infection. Discussion Altogether, our findings suggest that cHCV infection promotes cytotoxicity in CD8+ T cells regardless of virus specificity. The immunological changes caused by cHCV infection in CD8+ T cells may contribute to worsening the ongoing hepatic damage caused by HCV infection or exacerbate the immune response to possible co-infections. Our data provide a resource to groups exploring the underlying mechanisms of HCV-specific T cell spontaneous and treatment-induced resolution to inform the development of effective vaccines against HCV infection.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49361523","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 : 2023-06-14DOI: 10.3389/fviro.2023.1195717
Leidy Erandy Hernández-Magaña, Alfredo Mosqueda-Gracida, Víctor Javier Cruz-Holguín, M. Martínez-Castillo, E. Fuentes-Pananá, T. Rozmysłowicz, M. León-Juárez, Haruki Arévalo-Romero
Human Adenoviruses are a diverse family of viruses that can infect a variety of tissues causing acute or persistent infection. Viruses induce numerous cellular alterations as they hijack cellular functions to promote viral progeny. Recent research has shed light on the functions of viral proteins in orchestrating viral production, revealing that many of these functions overlap with oncogenesis or metabolic disruption. Studies of the Adenovirus family (Adenoviridae) have identified oncogenic members, such as Adenovirus (Ad-)2, 5, 9, and 12, and also Ad-36, which is most extensively studied for its ability to induce metabolic alterations. Specifically, Adenoviruses encode a gene product known as early region 4 open reading frame 1 (E4orf1), which has emerged as an oncoprotein and regulator of metabolism depending on the lineage of the infected host cell. This article aims to provide insight into the functions of the viral protein E4orf1 and the overlapping similarities between the oncogenic process and cell metabolism.
{"title":"E4orf1 as a key modulator in oncogenesis and of metabolism in Adenovirus infection","authors":"Leidy Erandy Hernández-Magaña, Alfredo Mosqueda-Gracida, Víctor Javier Cruz-Holguín, M. Martínez-Castillo, E. Fuentes-Pananá, T. Rozmysłowicz, M. León-Juárez, Haruki Arévalo-Romero","doi":"10.3389/fviro.2023.1195717","DOIUrl":"https://doi.org/10.3389/fviro.2023.1195717","url":null,"abstract":"Human Adenoviruses are a diverse family of viruses that can infect a variety of tissues causing acute or persistent infection. Viruses induce numerous cellular alterations as they hijack cellular functions to promote viral progeny. Recent research has shed light on the functions of viral proteins in orchestrating viral production, revealing that many of these functions overlap with oncogenesis or metabolic disruption. Studies of the Adenovirus family (Adenoviridae) have identified oncogenic members, such as Adenovirus (Ad-)2, 5, 9, and 12, and also Ad-36, which is most extensively studied for its ability to induce metabolic alterations. Specifically, Adenoviruses encode a gene product known as early region 4 open reading frame 1 (E4orf1), which has emerged as an oncoprotein and regulator of metabolism depending on the lineage of the infected host cell. This article aims to provide insight into the functions of the viral protein E4orf1 and the overlapping similarities between the oncogenic process and cell metabolism.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48739041","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 : 2023-06-08DOI: 10.3389/fviro.2023.1184095
Reca Marian Caballero, Ivonne González-Gamboa, S. Craig, N. Steinmetz
Plant virus-based nanoparticles (VNPs) offer a bioinspired approach to the delivery of drugs and imaging agents. The chemical addressability, biocompatibility, and scalable manufacturability of VNPs make them a promising alternative to synthetic delivery platforms. However, VNPs, just like other proteinaceous or synthetic nanoparticles (NPs), are readily recognized and cleared by the immune system and mechanisms such as opsonization and phagocytosis. Shielding strategies, such as PEGylation, are commonly used to mitigate premature NP clearance. Here, we investigated polyethylene glycol (PEG) coatings on the tobacco mosaic virus (TMV), which was used as a model nanocarrier system. Specifically, we evaluated the effects of linear and multivalent PEG coatings at varying chain lengths on serum protein adsorption, antibody recognition, and macrophage uptake. Linear and multivalent PEGs of molecular weights 2,000 and 5,000 Da were successfully grafted onto the TMV at ≈ 20%–60% conjugation efficiencies, and the degree of cross-linking as a function of PEG valency and length was determined. PEGylation resulted in the modulation of TMV–macrophage interactions and reduced corona formation as well as antibody recognition. Linear and multivalent PEG 5,000 formulations (but not PEG 2,000 formulations) reduced α-TMV antibody recognition, whereas shorter, multivalent PEG coatings significantly reduced α-PEG recognition—this highlights an interesting interplay between the NP and the PEG itself in potential antigenicity and should be an important consideration in PEGylation strategies. This work provides insight into the PEGylation of VNPs, which may improve the possibility of their implementation in clinical applications.
{"title":"Linear and multivalent PEGylation of the tobacco mosaic virus and the effects on its biological properties","authors":"Reca Marian Caballero, Ivonne González-Gamboa, S. Craig, N. Steinmetz","doi":"10.3389/fviro.2023.1184095","DOIUrl":"https://doi.org/10.3389/fviro.2023.1184095","url":null,"abstract":"Plant virus-based nanoparticles (VNPs) offer a bioinspired approach to the delivery of drugs and imaging agents. The chemical addressability, biocompatibility, and scalable manufacturability of VNPs make them a promising alternative to synthetic delivery platforms. However, VNPs, just like other proteinaceous or synthetic nanoparticles (NPs), are readily recognized and cleared by the immune system and mechanisms such as opsonization and phagocytosis. Shielding strategies, such as PEGylation, are commonly used to mitigate premature NP clearance. Here, we investigated polyethylene glycol (PEG) coatings on the tobacco mosaic virus (TMV), which was used as a model nanocarrier system. Specifically, we evaluated the effects of linear and multivalent PEG coatings at varying chain lengths on serum protein adsorption, antibody recognition, and macrophage uptake. Linear and multivalent PEGs of molecular weights 2,000 and 5,000 Da were successfully grafted onto the TMV at ≈ 20%–60% conjugation efficiencies, and the degree of cross-linking as a function of PEG valency and length was determined. PEGylation resulted in the modulation of TMV–macrophage interactions and reduced corona formation as well as antibody recognition. Linear and multivalent PEG 5,000 formulations (but not PEG 2,000 formulations) reduced α-TMV antibody recognition, whereas shorter, multivalent PEG coatings significantly reduced α-PEG recognition—this highlights an interesting interplay between the NP and the PEG itself in potential antigenicity and should be an important consideration in PEGylation strategies. This work provides insight into the PEGylation of VNPs, which may improve the possibility of their implementation in clinical applications.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47611962","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 : 2023-06-06DOI: 10.3389/fviro.2023.1180815
Natalie Winder, Z. Ashraf, Sara Gohar, Nada H. Baalbaki, Micheal Cork, S. Danby, M. Muthana
Background Washing hands with soap and lukewarm water for 20 s is a fundamental measure advocated especially within the UK to help control the spread of viral disease. However, these practices can induce irritant contact dermatitis, particularly in healthcare professionals (HCPs). HCPs typically manage their condition by replacing soap or alcohol-based hand sanitizers with cleansers containing mild surfactants and/or emollient ingredients [skin-friendly cleansers (SFCs)] to mitigate skin damage and/or using topical emollients after washing for repair. Despite this widespread practice, there is very limited evidence supporting the efficacy of these interventions in the prevention of viral propagation. Methodology Within this study a range of viruses comprising human coronavirus (HCoV), herpes simplex virus (HSV)-1, influenza (IVA), adenovirus (Ad), and murine norovirus (MNV) were tested against multiple hand wash products, including SFCs. In vitro analysis using plaque assays and tissue culture infectious dose 50 (TCID50) were used to assess virus infectability after incubation with the test products (soaps and SFCs) over a range of concentrations and time points. Transmission electron microscopy (TEM) was used to determine virus architecture and size, while viral replication genes were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results/conclusions Enveloped viruses demonstrated greater susceptibility over a range of test products, suggesting some SFCs are a suitable alternative to soap (depending on the presence of a viral envelope). However, no virucidal activity was observed for non-enveloped viruses. Water type (i.e., soft/hard) and pre-exposed hand hygiene conditions (i.e., clean/dirty) made little difference to the effectiveness of both soaps and SFCs. Therefore, new hand hygiene regimens should be implemented based on trying to encompass all viruses with varying structures, with specific emphasis on the absence of a viral envelope.
{"title":"Are mild cleansers appropriate for hand hygiene in the COVID era? An in vitro investigation of the antiviral efficacy of different hand hygiene products","authors":"Natalie Winder, Z. Ashraf, Sara Gohar, Nada H. Baalbaki, Micheal Cork, S. Danby, M. Muthana","doi":"10.3389/fviro.2023.1180815","DOIUrl":"https://doi.org/10.3389/fviro.2023.1180815","url":null,"abstract":"Background Washing hands with soap and lukewarm water for 20 s is a fundamental measure advocated especially within the UK to help control the spread of viral disease. However, these practices can induce irritant contact dermatitis, particularly in healthcare professionals (HCPs). HCPs typically manage their condition by replacing soap or alcohol-based hand sanitizers with cleansers containing mild surfactants and/or emollient ingredients [skin-friendly cleansers (SFCs)] to mitigate skin damage and/or using topical emollients after washing for repair. Despite this widespread practice, there is very limited evidence supporting the efficacy of these interventions in the prevention of viral propagation. Methodology Within this study a range of viruses comprising human coronavirus (HCoV), herpes simplex virus (HSV)-1, influenza (IVA), adenovirus (Ad), and murine norovirus (MNV) were tested against multiple hand wash products, including SFCs. In vitro analysis using plaque assays and tissue culture infectious dose 50 (TCID50) were used to assess virus infectability after incubation with the test products (soaps and SFCs) over a range of concentrations and time points. Transmission electron microscopy (TEM) was used to determine virus architecture and size, while viral replication genes were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results/conclusions Enveloped viruses demonstrated greater susceptibility over a range of test products, suggesting some SFCs are a suitable alternative to soap (depending on the presence of a viral envelope). However, no virucidal activity was observed for non-enveloped viruses. Water type (i.e., soft/hard) and pre-exposed hand hygiene conditions (i.e., clean/dirty) made little difference to the effectiveness of both soaps and SFCs. Therefore, new hand hygiene regimens should be implemented based on trying to encompass all viruses with varying structures, with specific emphasis on the absence of a viral envelope.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48408755","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 : 2023-06-06DOI: 10.3389/fviro.2023.1171108
M. Verheul, M. Hendriks, C. V. B. de Melo, Sophie van Tol, G. Godeke, R. van Binnendijk, W. Luytjes, C. Reusken, J. van Beek
Introduction Respiratory infections are a common cause of illness in older adults, potentially resulting in severe morbidity or mortality. While up to 10% of respiratory infections in this population are caused by one of the four human coronaviruses (hCoVs), OC43, HKU1, NL63, and 229E, data on hCoV epidemiological and immunological responses are limited in communitydwelling older adults. In addition, it is often difficult to distinguish and identify distinct hCoV infections. Therefore, both clinical characteristics and the possibility of using serology to identify recent infections were investigated. Methods Clinical characteristics and humoral immune responses were studied in community-dwelling older adults who presented with hCoV-related symptomatic influenza-like illness (ILI). Serum antibodies specific for each hCoV were identified by protein microarray using recombinant spike proteins. Result The symptoms of participants with molecular confirmation of hCoV infection were difficult to distinguish from symptoms of other viral pathogens causing ILI. Overall, severity based on a cumulative symptom score was less for hCoV than the other ILI-causing infections present in the study. Furthermore, symptom score did not correlate with changes in antibody levels. Using single serum samples to identify recent infections resulted in limited distinction among infections with receiver operating characteristic (ROC) area under the curve (AUC) values between 0.5 and 0.7, depending on the hCoV. However, paired serology samples collected at acute and recovery timepoints with an 8-week interval show an increase in type-specific antibodies with ROC AUC values between 0.78 and 0.96, depending on the hCoV. Discussion Although clinical characteristics are comparable between hCoVs, the analysis of antibody kinetics may provide an alternative method for identifying recent hCoV infections.
{"title":"Clinical and serological characteristics of symptomatic infection with seasonal human coronaviruses OC43, HKU1, NL63, and 229E in community-dwelling older adults","authors":"M. Verheul, M. Hendriks, C. V. B. de Melo, Sophie van Tol, G. Godeke, R. van Binnendijk, W. Luytjes, C. Reusken, J. van Beek","doi":"10.3389/fviro.2023.1171108","DOIUrl":"https://doi.org/10.3389/fviro.2023.1171108","url":null,"abstract":"Introduction Respiratory infections are a common cause of illness in older adults, potentially resulting in severe morbidity or mortality. While up to 10% of respiratory infections in this population are caused by one of the four human coronaviruses (hCoVs), OC43, HKU1, NL63, and 229E, data on hCoV epidemiological and immunological responses are limited in communitydwelling older adults. In addition, it is often difficult to distinguish and identify distinct hCoV infections. Therefore, both clinical characteristics and the possibility of using serology to identify recent infections were investigated. Methods Clinical characteristics and humoral immune responses were studied in community-dwelling older adults who presented with hCoV-related symptomatic influenza-like illness (ILI). Serum antibodies specific for each hCoV were identified by protein microarray using recombinant spike proteins. Result The symptoms of participants with molecular confirmation of hCoV infection were difficult to distinguish from symptoms of other viral pathogens causing ILI. Overall, severity based on a cumulative symptom score was less for hCoV than the other ILI-causing infections present in the study. Furthermore, symptom score did not correlate with changes in antibody levels. Using single serum samples to identify recent infections resulted in limited distinction among infections with receiver operating characteristic (ROC) area under the curve (AUC) values between 0.5 and 0.7, depending on the hCoV. However, paired serology samples collected at acute and recovery timepoints with an 8-week interval show an increase in type-specific antibodies with ROC AUC values between 0.78 and 0.96, depending on the hCoV. Discussion Although clinical characteristics are comparable between hCoVs, the analysis of antibody kinetics may provide an alternative method for identifying recent hCoV infections.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43338127","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 : 2023-06-02DOI: 10.3389/fviro.2023.1158703
J. Samal, Arjun Bhugra, V. Suroliya, P. Gautam, R. Agarwal, C. Bihari, E. Gupta
Despite the three years spent navigating the COVID-19 pandemic, scientists are still having to react to the disease due to the constant evolution of novel variants/subvariants. Over the last few months, a global plummet in COVID-19 cases has suggested we are transitioning towards endemic COVID-19. However, the new omicron offshoots (XBB variants) are driving a new surge of cases around the world. A few preliminary research findings suggest that the XBB.1.5 subvariant is more immune-evasive and displays higher binding to ACE2 human receptor than its other related omicron subvariants in circulation. In this first-of-its-kind report, we discuss a few XBB.1.5 cases and its clinical characteristics reported in Delhi State, North India.
{"title":"The emergence of the Omicron XBB.1.5 variant in India: a brief report on clinical presentation of a few cases","authors":"J. Samal, Arjun Bhugra, V. Suroliya, P. Gautam, R. Agarwal, C. Bihari, E. Gupta","doi":"10.3389/fviro.2023.1158703","DOIUrl":"https://doi.org/10.3389/fviro.2023.1158703","url":null,"abstract":"Despite the three years spent navigating the COVID-19 pandemic, scientists are still having to react to the disease due to the constant evolution of novel variants/subvariants. Over the last few months, a global plummet in COVID-19 cases has suggested we are transitioning towards endemic COVID-19. However, the new omicron offshoots (XBB variants) are driving a new surge of cases around the world. A few preliminary research findings suggest that the XBB.1.5 subvariant is more immune-evasive and displays higher binding to ACE2 human receptor than its other related omicron subvariants in circulation. In this first-of-its-kind report, we discuss a few XBB.1.5 cases and its clinical characteristics reported in Delhi State, North India.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47749925","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 : 2023-06-02DOI: 10.3389/fviro.2023.1157659
S. Mehta, D. Diak, B. Rooney, Stephanie S. Krieger, M. Nelman-Gonzalez, J. Locke, M. Nagel, M. Young, B. Crucian
Introduction Reactivation of herpes viruses, such as Epstein–Barr virus (EBV), herpes simplex virus 1 (HSV1), and varicella zoster virus (VZV), increases in astronauts during spaceflight, compared with their preflight and postflight levels. Reactivations can increase the risk of associated clinical conditions, such as herpes zoster, chronic neuropathic pain, vision loss, stroke, cognitive impairment, and cold sores. Furthermore, continued viral shedding for longer periods after space travel may increase the risk of viral transmission to uninfected crew contacts, including, but not limited to, the immunocompromised and newborn infants. Thus, it is essential to develop spaceflight countermeasures to prevent herpes viral reactivations to ensure the health of crewmembers and their contacts. One such countermeasure is the prophylactic administration of an antiviral drug (valacyclovir) against the alpha herpesviruses (VZV and HSV1). To determine the effectiveness of this countermeasure, we studied the shedding of EBV, VZV, and HSV1 in Antarctic expeditioners, who have similar salivary viral shedding patterns during winter-over to astronauts during long spaceflights. Methods The efficacy of this antiviral drug as a countermeasure was determined using three major parameters in the saliva of expeditioners during winter-over with and without administration of this drug: (i) viral load and frequency, (ii) physiological stress biomarkers [i.e., levels of cortisol, dehydroepiandrosterone (DHEA), and amylase), and (iii) immune markers (i.e., inflammatory cytokines)]. Thirty-two volunteers from two Antarctic stations (McMurdo and South Pole) participated in this study. Participants were randomly assigned to either the treatment group (valacyclovir HCl: 1 g/day) or placebo group (oyster calcium: 500mg/day). Results Viral shedding of EBV reduced significantly (> 24-fold) in the treatment group compared with the placebo group. HSV1 was also reduced by more than fivefold, but this was not statistically significant. No VZV shedding was observed in any of the participants. In the placebo group 50% of the saliva samples had measurable viral DNA (EBV, HSV1, or both), compared with 19% of the treatment group. There was no significant change in the ratio of cortisol to DHEA or levels of alpha-amylase, indicating that physiological stress was similar between the groups. No difference was detected in levels of salivary cytokines, except IL-10, which was found in significantly lower levels in the treatment group. Discussion These data indicate that valacyclovir is a safe and successful intervention to reduce EBV and HSV1 shedding in individuals subjected to extreme environments and stressors.
{"title":"Antiviral treatment with valacyclovir reduces virus shedding in saliva of Antarctic expeditioners","authors":"S. Mehta, D. Diak, B. Rooney, Stephanie S. Krieger, M. Nelman-Gonzalez, J. Locke, M. Nagel, M. Young, B. Crucian","doi":"10.3389/fviro.2023.1157659","DOIUrl":"https://doi.org/10.3389/fviro.2023.1157659","url":null,"abstract":"Introduction Reactivation of herpes viruses, such as Epstein–Barr virus (EBV), herpes simplex virus 1 (HSV1), and varicella zoster virus (VZV), increases in astronauts during spaceflight, compared with their preflight and postflight levels. Reactivations can increase the risk of associated clinical conditions, such as herpes zoster, chronic neuropathic pain, vision loss, stroke, cognitive impairment, and cold sores. Furthermore, continued viral shedding for longer periods after space travel may increase the risk of viral transmission to uninfected crew contacts, including, but not limited to, the immunocompromised and newborn infants. Thus, it is essential to develop spaceflight countermeasures to prevent herpes viral reactivations to ensure the health of crewmembers and their contacts. One such countermeasure is the prophylactic administration of an antiviral drug (valacyclovir) against the alpha herpesviruses (VZV and HSV1). To determine the effectiveness of this countermeasure, we studied the shedding of EBV, VZV, and HSV1 in Antarctic expeditioners, who have similar salivary viral shedding patterns during winter-over to astronauts during long spaceflights. Methods The efficacy of this antiviral drug as a countermeasure was determined using three major parameters in the saliva of expeditioners during winter-over with and without administration of this drug: (i) viral load and frequency, (ii) physiological stress biomarkers [i.e., levels of cortisol, dehydroepiandrosterone (DHEA), and amylase), and (iii) immune markers (i.e., inflammatory cytokines)]. Thirty-two volunteers from two Antarctic stations (McMurdo and South Pole) participated in this study. Participants were randomly assigned to either the treatment group (valacyclovir HCl: 1 g/day) or placebo group (oyster calcium: 500mg/day). Results Viral shedding of EBV reduced significantly (> 24-fold) in the treatment group compared with the placebo group. HSV1 was also reduced by more than fivefold, but this was not statistically significant. No VZV shedding was observed in any of the participants. In the placebo group 50% of the saliva samples had measurable viral DNA (EBV, HSV1, or both), compared with 19% of the treatment group. There was no significant change in the ratio of cortisol to DHEA or levels of alpha-amylase, indicating that physiological stress was similar between the groups. No difference was detected in levels of salivary cytokines, except IL-10, which was found in significantly lower levels in the treatment group. Discussion These data indicate that valacyclovir is a safe and successful intervention to reduce EBV and HSV1 shedding in individuals subjected to extreme environments and stressors.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46697203","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 : 2023-05-25DOI: 10.3389/fviro.2023.1181017
Litty Paul, Jocelynn Morgan, G. Pulley, Tirth Uprety, B. Hause, E. Ádám, Feng Li, C. Carter, D. Marthaler, E. Erol
Rotaviruses (RVs) are significant enteric pathogens of humans and animals. In March 2021, the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) received a fecal sample from a 1-week-old goat kid with diarrhea from a farm with 5 additional diarrheic kids. The fecal sample was tested negative for Bovine coronavirus, Bovine rotavirus Group A, E. coli K99+, Cryptosporidium parvum and Salmonella spp by multiplex real-time PCR assays. Interestingly, a novel Equine Rotavirus B (ERVB) in Kentucky was identified from neonatal foals also with watery diarrhea in the Spring of 2021. Once the ERVB-specific real-time PCR assay became available, the fecal sample from the goat kid was tested and found positive for RVB. Genome sequence of the caprine RVB from fecal sample was obtained using shotgun metagenomic sequencing by Illumina MiSeq. All of the eleven viral segments of caprine RVB were sequenced either completely or partially. Genetic and phylogenetic analysis of VP7, VP4, VP6, VP1–VP3, and NSP1- NSP5 genes indicated the caprine RVB strain had the genotype constellation of G3-P[3]-I3- R3-C3-M3-A4-N3-T3-E3-H3. In addition, the caprine RVB sequence showed the highest nucleotide identity and evolutionary relationship to the ERVB and previously sequenced caprine RVB strains. Given the similar geographical location of the equine and caprine strains from our study, these findings suggest a possible common source of infection.
{"title":"Genetic and phylogenetic relationship of an American caprine rotavirus B strain with equine rotavirus B","authors":"Litty Paul, Jocelynn Morgan, G. Pulley, Tirth Uprety, B. Hause, E. Ádám, Feng Li, C. Carter, D. Marthaler, E. Erol","doi":"10.3389/fviro.2023.1181017","DOIUrl":"https://doi.org/10.3389/fviro.2023.1181017","url":null,"abstract":"Rotaviruses (RVs) are significant enteric pathogens of humans and animals. In March 2021, the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) received a fecal sample from a 1-week-old goat kid with diarrhea from a farm with 5 additional diarrheic kids. The fecal sample was tested negative for Bovine coronavirus, Bovine rotavirus Group A, E. coli K99+, Cryptosporidium parvum and Salmonella spp by multiplex real-time PCR assays. Interestingly, a novel Equine Rotavirus B (ERVB) in Kentucky was identified from neonatal foals also with watery diarrhea in the Spring of 2021. Once the ERVB-specific real-time PCR assay became available, the fecal sample from the goat kid was tested and found positive for RVB. Genome sequence of the caprine RVB from fecal sample was obtained using shotgun metagenomic sequencing by Illumina MiSeq. All of the eleven viral segments of caprine RVB were sequenced either completely or partially. Genetic and phylogenetic analysis of VP7, VP4, VP6, VP1–VP3, and NSP1- NSP5 genes indicated the caprine RVB strain had the genotype constellation of G3-P[3]-I3- R3-C3-M3-A4-N3-T3-E3-H3. In addition, the caprine RVB sequence showed the highest nucleotide identity and evolutionary relationship to the ERVB and previously sequenced caprine RVB strains. Given the similar geographical location of the equine and caprine strains from our study, these findings suggest a possible common source of infection.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48348124","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 : 2023-04-28DOI: 10.3389/fviro.2023.1130171
Mario A. J. Golding, Nadia Khouri, Kathryn B Anderson, T. D. Wood, S. Sandiford
Latin America and the Caribbean continue to be adversely affected by dengue with the disease being endemic in several countries in this region. As a result, the social and economic impacts of the disease have risen significantly. Currently, there are very few solutions available to limit the spread of the virus, with vector control being the most commonly used. However, due to increased insecticidal resistance, scientists in the region have actively been seeking new ways to limit the spread of the virus. This quest has led researchers to investigate the antiviral properties of natural products. While antiviral screening activities focused on preventing or treating infection of the human host remains a significant area of study, some scientists have now focused their attention on preventing infection or transmission in the mosquito vector. This review therefore aims to highlight the use of natural products in Latin America and the Caribbean for blocking viral transmission of dengue virus in mosquito cells. This novel approach is promising and could ultimately be used in conjunction with other methods to help significantly reduce dengue incidence in the region.
{"title":"The use of natural products in Latin America and the Caribbean for blocking dengue infection in mosquito cells","authors":"Mario A. J. Golding, Nadia Khouri, Kathryn B Anderson, T. D. Wood, S. Sandiford","doi":"10.3389/fviro.2023.1130171","DOIUrl":"https://doi.org/10.3389/fviro.2023.1130171","url":null,"abstract":"Latin America and the Caribbean continue to be adversely affected by dengue with the disease being endemic in several countries in this region. As a result, the social and economic impacts of the disease have risen significantly. Currently, there are very few solutions available to limit the spread of the virus, with vector control being the most commonly used. However, due to increased insecticidal resistance, scientists in the region have actively been seeking new ways to limit the spread of the virus. This quest has led researchers to investigate the antiviral properties of natural products. While antiviral screening activities focused on preventing or treating infection of the human host remains a significant area of study, some scientists have now focused their attention on preventing infection or transmission in the mosquito vector. This review therefore aims to highlight the use of natural products in Latin America and the Caribbean for blocking viral transmission of dengue virus in mosquito cells. This novel approach is promising and could ultimately be used in conjunction with other methods to help significantly reduce dengue incidence in the region.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47309461","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}
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