Advances in Virology最新文献

Infections caused by human immunodeficiency virus (HIV) are considered one of the main public health problems worldwide. Antiretroviral therapy (ART) is the current modality of treatment for HIV-1 infection. It comprises the combined use of several drugs and can decrease the viral load and increase the CD4⁺ T cell count in patients with HIV-1 infection, thereby proving to be an effective modality. This therapy significantly decreases the rate of morbidity and mortality owing to acquired immunodeficiency syndrome (AIDS) and prolongs and improves the quality of life of infected patients. However, nonadherence to ART may increase viral resistance to antiretroviral drugs and transmission of drug-resistant strains of HIV. Therefore, it is necessary to continue research for compounds with anti-HIV-1 activity, exhibiting a potential for the development of an alternative or complementary therapy to ART with low cost and fewer side effects. Natural products and their derivatives represent an excellent option owing to their therapeutic potential against HIV. Currently, the derivatives of natural products available as anti-HIV-1 agents include zidovudine, an arabinonucleoside derivative of the Caribbean marine sponge (Tectitethya crypta), which inhibits the reverse transcriptase of the virus. This was the first antiviral agent approved for treatment of HIV infection. Additionally, bevirimat (isolated from Syzygium claviflorum) and calanolide A (isolated from Calophyllum sp.) are inhibitors of viral maturation and reverse transcription process, respectively. In the present review, we aimed to describe the wide repertoire of natural compounds exhibiting anti-HIV-1 activity that can be considered for designing new therapeutic strategies to curb the HIV pandemic.

In order to plan and execute proper preventative measures against COVID-19, we need to understand how SARS-CoV-2 is transmitted. It has been shown to remain infectious on surfaces from hours to days depending on surface type and environmental factors. The possibility of transmission through fur animals and contaminated pelts, along with the safety of those working with them, is a major concern. SARS-CoV-2 can infect minks and raccoon dogs and has spread to mink farms in numerous countries. Here, we studied the stability of SARS-CoV-2 on blue fox, Finn raccoon, and American mink pelt, fake fur, cotton, plastic, faux leather, and polyester and tested its inactivation by UV light and heat treatment. We detected infectious virus up to 5 days on plastic, up to 1 day on fake fur, less than a day on cotton, polyester, and faux leather, and even 10 days on mink fur. UV light failed to inactivate SARS-CoV-2 on pelts, most likely due to the mechanical protection by the fur. Hence, it should not be used to inactivate the virus on fur products, and its use for other surfaces should also be considered carefully. Heat treatment at 60°C for 1 h inactivated the virus on all surfaces and is a promising method to be applied in practice. This study helps prevent further spread of COVID-19 by increasing our understanding about risks of SARS-CoV-2 spread through contaminated clothing materials and giving important information needed to improve safety of those working in the production line as well as people using the products.

Background: The SARS-CoV-2 infection has caused one of the worst pandemics that history has ever known. SARS-CoV-2 can lead to multiple organ failure, which is life-threatening. Viral RNA is found in the lung, intestine, testicle, kidney, etc., which suggests the virus can be transmitted also via routes besides respiratory droplets. The aim of our study was to evaluate the presence of SARS-CoV-2 in urethral swabs.

Methods: We enrolled ten patients with SARS-CoV-2 infection who attended the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from March 2020 to April 2020. One urethral swab and one rhino-oropharyngeal swab were collected from each patient during SARS-CoV-2 infection.

Results: All ten patients had a negative urethral swab for SARS-CoV-2 RNA, whereas the rhino-oropharyngeal swab was positive for SARS-CoV-2 RNA. This finding demonstrates that, in our patients, the virus did not affect the urinary tract and therefore would not be found in the urine, and even more importantly, it would not be transmitted via urine. This result was independent of the stage of the disease.

Conclusion: If confirmed in larger studies, this observation could be the key to understanding the role of SARS-CoV-2 in relation to the genitourinary system.

Approximately 257 million people chronically infected with hepatitis B virus (HBV) worldwide are at risk of developing hepatocellular carcinoma (HCC). However, despite the availability of potent nucleoside/tide inhibitors, currently there are no curative therapies for chronic HBV infections. To identify potential new antiviral molecules, a select group of compounds previously evaluated in clinical studies were tested against 12 different viruses. Amongst the compounds tested, SRI-32007 (CYT997) demonstrated antiviral activity against HBV (genotype D) in HepG2.2.2.15 cell-based virus yield assay with 50% effective concentration (EC₅₀) and selectivity index (SI) of 60.1 nM and 7.2, respectively. Anti-HBV activity of SRI-32007 was further confirmed against HBV genotype B in huh7 cells with secreted HBe antigen endpoint (EC₅₀ 40 nM and SI 250). To determine the stage of HBV life cycle inhibited by SRI-32007, time of addition experiment was conducted in HepG₂-NTCP cell-based HBV infectious assay. Results indicated that SRI-32007 retained anti-HBV activity even when added 72 hours postinfection (72 h). Additional mechanism of action studies demonstrated potent inhibition of HBV core promoter activity by SRI-32007 with an EC₅₀ of 40 nM and SI of >250. This study demonstrates anti-HBV activity of a repurposed compound SRI-32007 through inhibition of HBV core promoter activity. Further evaluation of SRI-32007 in HBV animal models is needed to confirm its activity in vivo. Our experiments illustrate the utility of repurposing strategy to identify novel antiviral chemical leads. HBV core promoter inhibitors such as SRI-32007 might enable the development of novel therapeutic strategies to combat HBV infections.

Introduction: Studies on HPV prevalence in the head and neck region of South Africans are sparse. Of the available reports in the literature, there were no studies on the association between HPV-DNA presence in the mouth and oropharynx in relation to high-risk behaviours such as oral sex practice or tobacco and alcohol use.

Materials and methods: Following ethical clearance and informed consent, patients attending a regional HIV-management clinic and patients attending a dental hospital were recruited to this study. The participants completed an interview-based questionnaire obtaining demographic information, data on HIV serostatus, and behavioural data including sexual practices and tobacco and alcohol use, and a rinse-and-gargle specimen was taken. Specimens were analysed for HPV DNA on 3 separate PCR/qPCR platforms. Statistical analyses were performed for associations between the study group and categorical variables, HPV status, and data from the questionnaires.

Results: Of 221 participants, 149 were from a general population and 72 from the HIV-management clinic. Smokers comprised 29.4% of the sample, and 45.2% of participants reported to have ever used alcohol. Open mouth kissing during teenage years was confirmed by 64.7% of participants, 40.3% have given oral sex with their mouth, and 44.8% confirmed to have received oral sex from their partner's mouth. Seven participants (3.2%) had detectable α-HPV DNA, and 1 (0.4%) had detectable β-HPV DNA in their rinse-and-gargle specimens. Two participants were from the HIV-management clinic and 6 from the general dental population (overall 3.6%).

Conclusion: Five high-risk HPV, 2 low-risk HPV, and one β-HPV types were detected. The low prevalence of 3.6% compares well to similar studies in different cohorts studied in South Africa and falls within the global oral/oropharyngeal prevalence spectrum. Only 4 participants, all from the HIV-management clinic, had palatine tonsils. No significant relationships were found between HPV presence and demographic data or sexual, oral sexual, tobacco use, or alcohol use, and no associations were seen with numbers of sexual and oral-sex partners.

Background and aims: Direct-acting antivirals (DAAs) have made a revolution in hepatitis C virus (HCV) treatment with promising reduction of HCV infection and disease morbidities. However, unfortunately, treatment failure still occurs in about 5-15% of patients treated with DAA-based combination regimens. The primary aim of the study was to assess the efficacy and safety of a quadruple regimen of (sofosbuvir, daclatasvir, and simeprevir with a weight-based ribavirin) in chronic HCV DAAs-experienced patients.

Methods: This observational, open-label prospective study was carried out on 103 genotype 4 hepatitis C virus-infected patients who failed to achieve SVR12 after sofosbuvir-daclatasvir with or without ribavirin. Patients were treated for three months with sofosbuvir (400 mg), daclatasvir (60 mg), and simeprevir (150 mg) with a weight-based ribavirin dosage (1000-1200 mg/d). Response to treatment was determined by quantitative PCR for HCV at 3 months after the end of treatment (SVR12), and adverse events during the treatment were recorded.

Results: SVR was achieved in 100 patients (97.1%) at week 12 after treatment. No dangerous or life-threatening adverse events were recorded.

Conclusions: Retreatment of HCV genotype 4 patients with quadruple therapy is a good therapeutic option and achieves high response rates with minimal side effects.

Environmental water quality issues have dominated global discourse and studies over the past five decades. Significant parameters of environmental water quality include changes in biological and physical parameters. Some of the biological parameters of significance include occurrence of enteric viruses. Enteric viruses can affect both human and animal's health by causing diseases such as gastrointestinal and respiratory infections. In this study, the relationship between the occurrence of enteric viruses with reference to adenoviruses and enteroviruses and the physical water quality characteristics was assessed from water samples collected from Lake Victoria (LV) in Kenya. In order to understand the dynamics of season driven enteric viruses' contamination of the lake waters, we additionally analysed seasonal behavior of the lake's catchment area in terms of rainfall effects. Physical quality parameters were measured on-site while viral analysis was carried out by molecular methods using the nested polymerase chain reaction (nPCR). From 216 samples that were analysed for viral contamination, enteric viral genomes were discovered in 18 (8.3%) of the samples. Out of half of the samples (108) collected during the rainy season, enteric viral genomes were detected in 9.26% (10) while 8 (7.41%) samples tested positive from the other half of the samples (108) collected during the dry season. There was, however, no significant correlation noted between the physical water quality characteristics and the enteric viruses' occurrence. Neither wet season nor dry season was significantly associated with the prevalence of the viruses. In Lake Victoria waters, most of the samples had an average of physical water quality parameters that were within the range accepted by the World Health Organization (WHO) for surface waters with exemption of turbidity which was above the recommended 5 NTU as recorded from some sampling sites. Continuous and long-term surveillance of the lake water to accurately monitor the contaminants and possible correlation between chemical, physical, and biological characteristics is recommended. This would be important in continuous understanding of the hydrological characteristics changes of the lake for proper management of its quality with reference to the WHO standards. A multiple varied-sampling approach in different geographical regions during different seasons is recommended to establish the geographical distribution and relatedness to seasonal distribution patterns of the viruses. The data generated from this study will be useful in providing a basis for assessment of seasonally driven fecal pollution load of the lake and enteric virus contamination for proper management of the sanitary situation around the lake.

Background: Human norovirus (NoV) is an etiological agent associated with acute gastroenteritis (AGE) in both children and adults worldwide. However, very few studies have been reported on the prevalence and genetic diversity of NoV strains in children older than 5 years of age and adults with little or inadequate water and sanitation conditions.

Objectives: The aim of this study was assessing the prevalence of the human norovirus in older children and adults suffering with diarrhoea from rural communities in the Vhembe district, Limpopo province.

Methods: Between August 2017 and October 2018, stool samples were collected from outpatients suffering from AGE and screened for NoV strains using the RIDA©GENE norovirus I and II real-time one-step RT-PCR. RNA extracts of NoV-positive samples were subjected to RT-PCR amplification and nucleotide sequencing to genotype the positive NoV strains.

Results: Out of 80 collected stool samples, 13 (16%) were tested positive for norovirus. Genogroup GII was identified in 6/13 (46%) samples and genogroup GI in 7/13 (54%) samples. The sequence analyses showed multiple genotypes including GII.Pg, GII.1, GII.2, GII.4, and GI.3. Phylogenetic analysis revealed the relatedness of NoV genotypes identified with other strains reported globally.

Conclusion: Continued systematic surveillance to evaluate norovirus association with diarrhoea is needed to assist with epidemiological surveillance and disease burden in people of all the age groups.

Alcohol use disorder (AUD) patients comorbid with hepatitis C virus (HCV) infection (HCV + AUD) could have progressively severe clinical sequels of liver injury and inflammation. Serum zinc and several polyunsaturated fatty acids (PUFAs) get dysregulated in AUD as well as HCV. However, the extent of dysregulation of PUFAs and zinc deficiency and their interaction in HCV + AUD as a comorbid pathology has not been studied. We examined the role of dysregulation of FAs and low zinc in HCV + AUD patients. 138 male and female participants aged 21-67 years were grouped as HCV-only (Gr. 1; n = 13), HCV + AUD (Gr. 2; n = 25), AUD without liver injury (Gr. 3; n = 37), AUD with liver injury (Gr. 4; n = 51), and healthy volunteers (Gr. 5 or HV; n = 12). Drinking history, individual demographic measures, fasting fatty acids, liver function, and zinc were measured and analyzed. HCV + AUD patients showed the highest ALT level compared to the rest of the groups. Serum zinc concentrations were the lowest, and the proinflammatory shift was the highest (characterized by ω6 : ω3 ratio) in the HCV + AUD patients. Total ω3, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) were the lowest in HCV + AUD patients. Total ω3, α-linoleic acid (α-LA) along with covariable number of drinking days past 90 days (NDD90), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) independently showed significant association with low zinc in the HCV + AUD patients. Heavy drinking pattern showed that NDD90 has a significant mediating role in the representation of the relationship between candidate ω3 PUFAs and zinc uniquely in the HCV + AUD patients. Low serum zinc showed a distinctively stronger association with total and candidate ω3s in the HCV + AUD patients compared to the patients with HCV or AUD alone, supporting dual mechanism involved in the exacerbation of the proinflammatory response in this comorbid cohort. This trial is registered with NCT#00001673.