Virus-related Factors Research Articles

Global pattern and determinant for interaction of seasonal influenza viruses

BackgroundThe prevalence of different types/subtypes varies across seasons and countries for seasonal influenza viruses, indicating underlying interactions between types/subtypes. The global interaction patterns and determinants for seasonal influenza types/subtypes need to be explored. MethodsInfluenza epidemiological surveillance data, as well as multidimensional data that include population-related, environment-related, and virus-related factors from 55 countries worldwide were used to explore type/subtype interactions based on Spearman correlation coefficient. The machine learning method Extreme Gradient Boosting (XGBoost) and interpretable framework SHapley Additive exPlanation (SHAP) were utilized to quantify contributing factors and their effects on interactions among influenza types/subtypes. Additionally, causal relationships between types/subtypes were also explored based on Convergent Cross-mapping (CCM). ResultsA consistent globally negative correlation exists between influenza A/H3N2 and A/H1N1. Meanwhile, interactions between influenza A (A/H3N2, A/H1N1) and B show significant differences across countries, primarily influenced by population-related factors. Influenza A has a stronger driving force than influenza B, and A/H3N2 has a stronger driving force than A/H1N1. ConclusionThe research elucidated the globally complex and heterogeneous interaction patterns among influenza type/subtypes, identifying key factors shaping their interactions. This sheds light on better seasonal influenza prediction and model construction, informing targeted prevention strategies and ultimately reducing the global burden of seasonal influenza.

Clinical Characteristics and Outcomes of AIDS-Related Burkitt Lymphoma in China: A Retrospective Single-Center Study.

Objectives: Studies on the prognosis and risk stratification of patients with acquired immune deficiency syndrome (AIDS) - related Burkitt lymphoma (AR-BL) are rare. We aim to construct a novel model to improve the risk assessment of these patients. Methods: We retrospectively analyzed the clinical data of 34 patients over the past 10 years and the factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Then, the novel model consisting of screened factors was compared with the existing models. Results: With a 37-month median follow-up, the overall 2-year PFS and OS rates were 40.50% and 36.18%, respectively. The OS of patients who received chemotherapy was better compared with those without chemotherapy (P = .0012). Treatment with an etoposide, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin-based regimen was associated with longer OS and PFS compared with a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen (OS, P = .0002; PFS, P = .0158). Chemotherapy (hazard ratio [HR] = 0.075; 95% confidence interval [CI], 0.009-0.614) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 to 4 (HR = 4.738; 95% CI, 1.178-19.061) were independent prognostic factors of OS in multivariate analysis and we established a novel prognostic risk stratification model named GZ8H model with chemotherapy and ECOG PS. Conclusion: GZ8H showed better stratification ability than the international prognostic index (IPI) or Burkitt lymphoma IPI (BL-IPI). Furthermore, the C-index of the nomogram used to predict OS was 0.884 in the entire cohort and the calibration curve showed excellent agreement between the predicted and actual results of OS. No human immunodeficiency virus-related factors were found to be associated with OS and PFS of AR-BL patients in our study. Overall, the clinical characteristics and outcomes in AR-BL were shown and prognostic factors for OS and PFS were identified in this study.

P16 and p53 can Serve as Prognostic Markers for Head and Neck Squamous Cell Carcinoma

ObjectiveThe present study aimed to explore the expression and clinical significance of human papilloma virus-related pathogenic factors (p16, cyclin D1, p53) in patients with head and neck squamous cell carcinoma (HNSCC) and construct a predictive model. MethodsThe Cancer Genome Atlas was used to obtain clinical data for 112 patients with HNSCC. Expression of p16, p53, and cyclin D1 was quantified. We used the survival package of the R program to set the cut-off value. Values above the cut-off were considered positive, while values below the cut-off were negative. Kaplan–Meier analysis and univariate and multivariate Cox regression analyses were performed to investigate prognostic clinicopathological indicators and the expression of p16, p53, and cyclin D1. A predictive model was constructed based on the results of multifactor Cox regression analysis, and the accuracy of the predictive model was verified through final calibration analysis. Follow-up of patients with HNSCC at the Affiliated Hospital of Binzhou Medical University was conducted from 2015 to 2017, and reliability of the predictive model was validated based on follow-up data and molecular expression levels. ResultsAccording to the results, expression of p16 and p53 was significantly associated with prognosis (P < .05). The predictive model constructed based on the expression levels of p16 and p53 was useful for evaluating the prognosis of patients with HNSCC. The predictive model was validated using follow-up data obtained from the hospital, and the trend of the follow-up results was consistent with the predictive model. Conclusionp16 and p53 can be used as key indicators to predict the prognosis of HNSCC patients and as critical immunohistochemical indicators in clinical practice. The survival model constructed based on p16 and p53 expression levels reliably predicts patient prognosis.

Evaluation of Glomerular Filtration Rate Trends in People Living With HIV Corrected by the Baseline Glomerular Filtration Rate.

Chronic kidney disease, for which estimated glomerular filtration rate (eGFR) trajectories are early markers, is frequent in people living with HIV. Identify eGFR trajectory patterns according to kidney function and assess associated factors over a 13-year follow-up period. We evaluated longitudinal changes and its associated factors in eGFR of 3366 participants according to kidney function with a 2-level, linear, mixed model. Participants with initial kidney dysfunction experienced a slight eGFR increase, whereas others showed a slight decrease. A weak relationship was observed between baseline eGFR and its variation over time. Baseline eGFR was affected by age, CD4 + count, viral load, hypertension, hyperlipidemia, AIDS-defining illness and tenofovir (TDF) with integrase inhibitor (INSTI) or efavirenz. Significant factors for eGFR change included the following: in kidney dysfunction, CD4 + cell count of >350 cells per cubic millimeter and undetectable viral load increased eGFR, whereas TDF + protease inhibitor decreased eGFR; in mildly decreased kidney function, CD4 + cell count of >350 cells per cubic millimeter, AIDS-defining illness, and TDF + efavirenz increased eGFR, whereas age, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR; in normal kidney function, age, CD4 + cell count of > 350 cells per cubic millimeter, undetectable viral load, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR, whereas TDF + efavirenz increased eGFR (all P value for interaction < 0.05). Our findings suggest that eGFR trajectories varied widely between individuals in people living with HIV. In the lower eGFR group, virus-related factors were more relevant, whereas traditional risk factors for renal dysfunction were more prominent in the highest eGFR group.

Impacting factors and sources of perceived stress by home-quarantined residents in Shanghai during COVID-19 epidemic

BackgroundHome-quarantine is one of the most common measures implemented to prevent or minimize the transmission of COVID-19 among communities. This study assessed stress levels of the home-quarantined residents in Shanghai during a massive wave of COVID-19 epidemic this year, explored the stress sources perceived by the respondents, and analyzed the association between each of the sociodemographic factors and the stress level.MethodsThis online survey was launched during April 23 - 30, 2022, the early stage of a massive wave of COVID-19 in Shanghai, China. Participants were quarantined-residents negative for COVID-19. They were asked to list some situations that were their major concerns and perceived stressful, in addition to sociodemographic and COVID-19 related information. Moreover, they were asked to complete the Perceived Stress Scale-14 (PSS-14) for the assessment of stress level.ResultsA total of 488 valid questionnaires were collected from 192 male and 296 female respondents. Overall, 207 persons (42.42%) presented high stress level (PSS-14 score ≥43). The top three concerns perceived stressful by respondents are “not allowed to go outdoors”, “uncertain duration of the epidemic”, and “lack of food supply”. Fewer than 50% of the respondents perceived the other situations stressful. Higher proportions of young adults (≤ 29 years old), males, unemployed, singles, and those with low income (≤ 1999 yuan/month) perceived high stress compared to their counterparts, none of COVID-19 related factors is associated with the stress level, including location of residence, result of nucleic acid test, knowledge about COVID-19, whether vaccinated, and quarantine duration.ConclusionHome-quarantine applied to people negative for COVID-19 led to a lot of major concerns that may be perceived stressful, whereas the virus-related factors did not show significant impact on mental health of the respondents.

Metabolic-associated fatty liver disease is associated with low muscle mass and strength in patients with chronic hepatitis B.

BACKGROUNDAlthough the prognostic relevance of sarcopenia has been increasingly recognised in the context of liver disease, there is a paucity of data evaluating body composition in patients with chronic hepatitis B (CHB). Beyond virus-related factors, nutritional and metabolic aspects can be associated with skeletal muscle abnormalities in these patients and should not be disregarded.AIMTo evaluate the association between components of sarcopenia and demographic, clinical, lifestyle, nutritional, and biochemical variables in CHB patients.METHODSDual-energy X-ray absorptiometry (DXA) was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for body mass index (ALMBMI). Muscle function was evaluated by hand grip strength (HGS) and the timed up and go test. Metabolic-associated fatty liver disease (MAFLD) was defined according to the criteria proposed by an international expert panel. A body shape index and the International Physical Activity Questionnaire were used to assess central obesity and physical activity level, respectively.RESULTSThis cross-sectional study included 105 CHB outpatients followed at the tertiary care ambulatory centre (mean age, 48.5 ± 12.0 years; 58.1% males; 76.2% without cirrhosis; 23.8% with compensated cirrhosis). The DXA-derived fat mass percentage was inversely correlated with the ALMBMI (r = - 0.87) and HGS (r = - 0.63). In the multivariable analysis, MAFLD, sedentarism and central obesity were positively and independently associated with low ALMBMI. MAFLD and central obesity were independently associated with low HGS.CONCLUSIONMAFLD and central obesity were associated with low muscle mass and strength in patients with chronic hepatitis B, independent of the liver disease stage.

Innate Immune Responses by Respiratory Viruses, Including Rhinovirus, During Asthma Exacerbation.

Viral infection, especially with rhinovirus (RV), is a major cause of asthma exacerbation. The production of anti-viral cytokines such as interferon (IFN)-β and IFN-α from epithelial cells or dendritic cells is lower in patients with asthma or those with high IgE, which can contribute to viral-induced exacerbated disease in these patients. As for virus-related factors, RV species C (RV-C) induces more exacerbated disease than other RVs, including RV-B. Neutrophils activated by viral infection can induce eosinophilic airway inflammation through different mechanisms. Furthermore, virus-induced or virus-related proteins can directly activate eosinophils. For example, CXCL10, which is upregulated during viral infection, activates eosinophils in vitro. The role of innate immune responses, especially type-2 innate lymphoid cells (ILC2) and epithelial cell-related cytokines including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), in the development of viral-induced airway inflammation has recently been established. For example, RV infection induces the expression of IL-33 or IL-25, or increases the ratio of ILC2 in the asthmatic airway, which is correlated with the severity of exacerbation. A mouse model has further demonstrated that virus-induced mucous metaplasia and ILC2 expansion are suppressed by antagonizing or deleting IL-33, IL-25, or TSLP. For treatment, IFNs including IFN-β suppress not only viral replication but also ILC2 activation in vitro. Agonists of toll-like receptor (TLR) 3 or 7 can induce IFNs, which can then suppress viral replication and ILC2 activation. Therefore, if delivered in the airway, IFNs or TLR agonists could become innovative treatments for virus-induced asthma exacerbation.

Host-virus interactions in PK-15 cells infected with Pseudorabies virus Becker strain based on RNA-seq

Pseudorabies is a highly contagious viral disease caused by the pseudorabies virus (PRV), and it is one of the most devastating diseases for the swine industry worldwide. However, the host-virus interaction and virus-related host factors at the mRNA level in virus natural host (pig) cells, are not fully understood. Here, we performed time-course RNA sequencing of the PK-15 cells infected with a recombinant strain PRV-Becker-GFP to study the dynamic competition between the host and the virus. At early stage of infection (3 hpi), our results suggested that the activation of cytosolic DNA-sensing pathway and NOD-like receptor signaling pathway might play a role in recognition of PRV, and the activation of NF-kappa B signaling pathway and TNF signaling pathway might be involved in immune response against the virus. However, all these pathways were subsequently inhibited by PRV. Additionally, our data indicated the fatty acid degradation pathway was significantly downregulated during late stage of infection (9 hpi), which was likely to accumulate fatty acids for viral envelope synthesis. Moreover, we verified the expression of 5 representative genes (ALDH1B1, ACAA2, ACSL3, ADH5, and EHHADH) related to fatty acid degradation pathway by RT-qPCR. Overall, our findings provide valuable information to better understand host-virus interactions and the immune escape mechanism of PRV-Becker as a virulent strain, offering novel targets for porcine anti-PRV breeding research and potential clinical treatment.

575. Local Experience of Breakthrough SARS-CoV-2 Infections After Full Vaccination

BackgroundSARS-CoV-2 the etiology of COVID-19 has caused more than 33 million cases and almost 600,000 deaths in the United States alone. Vaccination is a vital tool in controlling the pandemic. With accelerated infection rates in various parts of the world, the incidence of variants has risen and threatens to set back the long sought after immunity, provided by available vaccines. The objective of this study was to evaluate the breakthrough infection rate after complete vaccination, in Sangamon County, with a rural and urban population of 195,000 in Central Illinois.MethodsData regarding breakthrough infections collected from the Sangamon County Department of Public Health, included the total number of infections, time after vaccination, age range of those infected and the type of vaccine used. Complete vaccination was defined as 14 days after the single dose of Johnson & Johnson/Janssen or the second dose of Pfizer-BioNTech or Moderna Inc. vaccine.ResultsVaccineInfections% of BreakthroughPfizer-BioNTech1443.75Moderna, Inc.1031.25Johnson & Johnson/Janssen825Total32100The number of fully vaccinated individuals at the time of writing of this study was 87,086 which corresponded to 44.58 % of the total population. The breakthrough infection percentage was calculated as 0.036%. The mean time after vaccination to infection was 49.13 days with a standard deviation of 23.28.ConclusionBreakthrough infections among fully vaccinated individuals in our county, have been quite rare, which points to the high efficacy of the vaccines. A complex number of factors likely contribute to this including virus-related factors i.e. variant forms and specific patient-related factors which are not a part of this study. The afore-mentioned high efficacy rate of the vaccines provides further justification, to continue to pursue a persistent vaccination strategy to mitigate the effects of the SARS-CoV-2 virus.Disclosures All Authors: No reported disclosures

Phase angle is associated with sarcopenia and its components in patients with chronic hepatitis c

Rationale: Sarcopenia is a remarkable finding in patients with chronic hepatitis C (CHC). However, the potential factors behind the skeletal muscle loss have not been completely clarified. We evaluate independent associations between host-, disease-, nutritional- and virus-related factors with sarcopenia and its components [appendicular muscle mass index (ASMI) and handgrip strength (HGS)]. Additionally, we appraised the association between sarcopenia and Bioelectrical Impedance Analysis (BIA)-derived phase angle (PhA).

Experimental Assessment of Possible Factors Associated with Tick-Borne Encephalitis Vaccine Failure.

Currently the only effective measure against tick-borne encephalitis (TBE) is vaccination. Despite the high efficacy of approved vaccines against TBE, rare cases of vaccine failures are well documented. Both host- and virus-related factors can account for such failures. In this work, we studied the influence of mouse strain and sex and the effects of cyclophosphamide-induced immunosuppression on the efficacy of an inactivated TBE vaccine. We also investigated how an increased proportion of non-infectious particles in the challenge TBE virus would affect the protectivity of the vaccine. The vaccine efficacy was assessed by mortality, morbidity, levels of viral RNA in the brain of surviving mice, and neutralizing antibody (NAb) titers against the vaccine strain and the challenge virus. Two-dose vaccination protected most animals against TBE symptoms and death, and protectivity depended on strain and sex of mice. Immunosuppression decreased the vaccine efficacy in a dose-dependent manner and changed the vaccine-induced NAb spectrum. The vaccination protected mice against TBE virus neuroinvasion and persistence. However, viral RNA was detected in the brain of some asymptomatic animals at 21 and 42 dpi. Challenge with TBE virus enriched with non-infectious particles led to lower NAb titers in vaccinated mice after the challenge but did not affect the protective efficacy.

Diagnostic and prognostic significance of hepatic steatosis in patients with chronic hepatitis C.

Knowing that hepatic steatosis (HS) is a common occurrence in patients with chronic hepatitis C (CHC), it is essential to establish what are the factors that predispose to its occurrence and what is the role of HS in the evolution and prognosis of patients with CHC who develop this feature. To achieve these aims, we performed a retrospective clinical study in 33 patients with CHC hospitalized, diagnosed, and monitored in the 2nd Medical Department of the Emergency County Hospital, Craiova, Romania, in a period of two years (2011–2012). Following clinical, hematological, biochemical, immunological, and pathological investigations of the 33 patients with CHC selected, only 14 patients showed pathological changes of the HS. The appearance of steatosis in patients with CHC results from a complex interaction between the particularities of the host and viral factors. The main risk factors of the host, which contributed to the appearance of HS were sex, age, body mass index (BMI), body weight, and personal history of pathology (obesity, metabolic syndrome). Virus-related factors involved in HS were viremia and viral genotype. In conclusion, HS is a common finding (42.42%) in patients with CHC, particularly genotypes 1 and 2. Early detection of HS by invasive or non-invasive methods is an important objective of monitoring patients with CHC, because HS is correlated with a high degree of fibrosis. Therefore, early correction of metabolic factors and early introduction of antiviral therapy are important targets for treating of patients with CHC.

Downregulation of hepatitis C virus replication by miR-196a using lentiviral vectors.

Hepatitis C virus (HCV) is a positive-sense, single-stranded RNA virus that causes chronic hepatitis and hepatocellular carcinoma. Cellular microRNAs (miRNAs) directly modulate the viral infectivity and indirectly through targeting virus-related host factors. They play an essential role in the progression of different stages of HCV infection. The roles of miR-196 family in HCV infection and hepatocellular carcinoma progression remain poorly understood. Using ViTa databases, miR-196a as a high-score miRNA targeting the NS5 A region of HCV genome was selected. Using dual luciferase assay and an established cell-cultured HCV (HCVcc) system, the effect of miR-196a on HCV genome was assessed. In silico analysis demonstrated the significant role of miR-196a in the downregulation of HCV replication. Using dual luciferase assay, the liver-specific miR-196a and NS5 A gene binding was confirmed. To assess the experimental role of miR-196a, an HCVcc system was established in the Huh 7.5 cell lines. The HCV-RNA 1b derived from an infected patient was transfected into Huh 7.5 cells containing miR-196a lentiviral vectors (Huh 7.5/miR-196a), mocks (Huh 7.5/mock vector), and naïve Huh 7.5 cells. The rate of reduction of the HCV genome replication was assessed using relative real-time PCR assay. These results represent miR-196a overexpression and its roles in regulating HCV genome replication. However, miR-196a may inhibit HCV replication and accelerate the early stages of apoptosis. Overexpression of miR-196a in Huh 7.5 replicon cell is a potential new strategy to prevent hepatitis C infection. The results of this study suggest that miR-196a directly downregulates HCV replication and may serve as a new antiviral therapy.

Common evolutionary features of the envelope glycoprotein of HIV-1 in patients belonging to a transmission chain

The diversity of the HIV-1 envelope glycoproteins (Env) is largely a consequence of the pressure exerted by the adaptive immune response to infection. While it was generally assumed that the neutralizing antibody (NAb) response depended mainly on the infected individual, the concept that virus-related factors could be important in inducing this response has recently emerged. Here, we analyzed the influence of the infecting viral strain in shaping NAb responses in four HIV-1 infected subjects belonging to a transmission chain. We also explored the impact of NAb responses on the functional evolution of the viral quasispecies. The four patients developed a strong autologous neutralizing antibody response that drove viral escape and coincided with a parallel evolution of their infecting quasispecies towards increasing infectious properties, increasing susceptibility to T20 and increasing resistance to both CD4 analogs and V3 loop-directed NAbs. This evolution was associated with identical Env sequence changes at several positions in the V3 loop, the fusion peptide and the HR2 domain of gp41. The common evolutionary pattern of Env in different hosts suggests that the capacity of a given Env to adapt to changing environments may be restricted by functional constraints that limit its evolutionary landscape.

Re-treatment of Hepatitis C Infection After Multiple Failures of Direct-Acting Antiviral Therapy.

BackgroundDirect-acting antiviral (DAA) therapies for hepatitis C virus (HCV) result in initial cure rates of 95% to 99% and re-treatment cure rates of 95%. Nevertheless, given the sheer magnitude of infected persons, some will ultimately fail multiple DAA therapies, and re-treatment of these persons has not been adequately studied. MethodsWe evaluated treated an HIV-infected man with cirrhosis from genotype 1b HCV who had failed 3 DAA regimens.ResultsWe treated and cured our “particularly difficult-to-cure” patient with sofosbuvir plus glecaprevir/pibrentasvir plus ribavirin for 24 weeks. We discuss the literature on potential biological factors behind his treatment failures such as lack of HCV seroconversion during his infection course, and multiple failures of hepatitis B seroconversion after vaccination, and the rationale for choosing his curative salvage regimen.DiscussionThere are no clinical trials-proven re-treatment regimens for “particularly difficult-to-cure” patients. Multiple patient- and virus-related factors that do not affect cure rates in treatment-naive patients may need to be considered in choosing a re-treatment regimen for these patients. These regimens may need to include combinations drugs that are not available in single-tablet form, addition of ribavirin, and longer durations of treatment than standard.

Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs.

Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

Physiopathology of HIV-2infection

The HIV-2virus is not widely spread worldwide, with only one to three million infected people, mainly in West Africa. HIV-2is responsible for an attenuated infection compared to HIV-1. Thus, HIV-2infection is characterized by low and frequently undetectable viral loads and a slower course to AIDS. Describing the infection natural history differences between these two viruses, and then determining the mechanisms underlying the HIV-2lower pathogenicity, is essential to identify the mechanisms underlying the immunopathogenicity of HIV infection. Studies conducted to date have identified both host-related and virus-related factors contributing to an improved immune control and the attenuated viral replication. In this review, we summarize the origins and epidemiology of HIV-2, the natural history of infection, the main virological tools for monitoring the infection course, and the main mechanisms explaining the attenuated infection of HIV-2. We also indicate the points remaining to be explored.

Hepatitis C virus genotype 3a: Predictive factors associated with treatment response in patients of Peshawar.

Hepatitis C Virus (HCV) is a flavivirus responsible for causing chronic liver diseases including cirrhosis and hepatocellular carcinoma. Identification of various patient and virus-related factors that can help predict response to antiviral therapy is extremely important in formulating the best therapeutic strategy for each patient either to continue or stop the therapy. The present study aimed to determine Sustained Virological Response (SVR) in HCV genotype 3a infected patients that received combination therapy of Sofosbuvir and Ribavirin and to investigate various factors that can help predict SVR. Study Design: Longitudinal Study Settings: Institute of basic Medical Sciences, Khyber Medical University, Peshawar (IBMS, KMU). Period: July 2016 to September 2017. Materials and Methods: Treatment response was evaluated among 100 HCV genotype 3a infected patients that received Sofosbuvir and Ribavirin therapy for 24 weeks. Various baseline parameters including hematological, biochemical and viral profiles of were recorded. HCV genotype determination was carried out by type specific nested PCR based genotyping assay. Viral load was determined at baseline, at 12 weeks for Early Virological Response (EVR) and at 24 weeks of treatment for SVR. Viral RNA quantification was carried out by Real Time PCR. Results: Out of 100 patients, SVR was observed in 83% of patients; while 17% of the chronic HCV 3a infected patients were Non-Responders (NR). Mean age of patients was low 34 ± 9.8 among patients who achieved SVR as compared to patients with non-response (41 ± 10). The 24 weeks Alanine aminotransferase (ALT) levels were significantly lower among patients with SVR (p-value ≤ 0.05). Although statistically not significant, baseline viral load was higher in NR group (p-value ≥ 0.05), than those with SVR. Association of EVR with SVR was found statistically significant (OR= 2.8, 95% CI 1.2-6.4, p-value ≤ 0.05). Conclusions: The current study indicated that pre and on-treatment monitoring of patients receiving anti-viral therapy is important for the management of patients with chronic HCV infection.

Hepatitis C virus-related factors associated WITH cognitive performance in HIV-HCV-coinfected patients.

The contribution of HCV-related variables to cognitive impairment in HIV-HCV-coinfected patients has been poorly investigated. We selected HIV-HCV-coinfected patients undergoing cognitive examination (exploring memory, language, speed of mental processing and fine motor function) at three clinical centres. Cognitive performance was evaluated using Z-transformed scores. Logistic regression analysis was used to investigate variables associated to cognitive impairment (defined as a composite Z-score ≤ - 1). Overall, 146 HIV-HCV-coinfected patients were enrolled. Median HCV-RNA was 6.2logU/mL. HCV genotype 1a/b was the most represented (53.4%). Liver fibrosis was mild (Fib4 ≤ 1.45) in the majority of patients (44.5%). Global cognitive impairment was diagnosed in 35 (24%) subjects. Exploring each domain, a higher proportion of impairment was observed for memory (37%) followed by speed of mental processing (32.2%), fine motor functioning (24%) and language (18.5%). Among HCV-related variables, the duration of HCV infection was independently associated with global cognitive impairment (aOR 1.13 per +1year, p= 0.016) and abnormal speed of mental processing (aOR 1.16 per +1year, p= 0.001), while higher HCV-RNA was independently associated to fine motor functioning impairment (aOR 1.98 per +1log, p= 0.037). HCV genotype, fibrosis stage, transaminases or bilirubin levels were not related to cognitive performance. Of note, integrase inhibitor (InSTI) use was independently associated to a pathological performance in fine motor functioning (aOR 3.34, p= 0.035) and memory (aOR 3.70, p= 0.014). In conclusion, the duration of HCV infection and HCV-RNA load showed an association with cognitive impairment, suggesting a role of hepatitis-related factors in the development of cognitive disorders in HIV-HCV-coinfected patients. The association between InSTI use and altered cognitive performance should prompt investigations about potential neurotoxicity of these drugs.

Genomic characterization of hepatitis C virus transmitted founder variants with deep sequencing

Transfer of hepatitis C virus (HCV) infection from a donor to a new recipient is associated with a bottleneck of genetic diversity in the transmitted viral variants. Existing data suggests that one, or very few, variants emerge from this bottleneck to establish the infection (transmitted founder [T/F] variants). In HCV, very few T/F variants have been characterized due to the challenges of obtaining early infection samples and of high throughput viral genome sequencing.This study used a large, acute HCV, deep-sequenced dataset from first viremia samples collected in nine prospective cohorts across four countries, to estimate the prevalence of single T/F viruses, and to identify host and virus-related factors associated with infections initiated by a single T/F variant. The short reads generated by Illumina sequencing were used to reconstruct viral haplotypes with two haplotype reconstruction algorithms. The haplotypes were examined for random mutations (Poisson distribution) and a star-like phylogeny to identify T/F viruses. The findings were cross-validated by haplotype reconstructions across three regions of the genome (Core-E2, NS3, NS5A) to minimize the possibility of spurious overestimation of single T/F variants.Of 190 acute infection samples examined, 54 were very early acute infections (HCV antibody negative, RNA positive), and single transmitted founders were identified in 14 (26%, 95% CI: 16–39%) after cross validation across multiple regions of the genome with two haplotype reconstruction algorithms. The presence of a single T/F virus was not associated with any host or virus-related factors, notably viral genotype or spontaneous clearance.In conclusion, approximately one in four new HCV infections originates from a single T/F virus. Resolution of genomic sequences of single T/F variants is the first step in exploring unique properties of these variants in the infection of host hepatocytes.