Abstract
HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.
Highlights
Infection with hepatitis C virus (HCV) becomes chronic in around 60-80% of patients (Santantonio et al, 2008)
Plasma samples from four patients recently infected with HCV were studied; all were HIV1 infected men who have sex with men (MSM)
HCV infection was acquired by sexual transmission in all patients and there was no history of injecting drug use or other parenteral exposure
Summary
Infection with hepatitis C virus (HCV) becomes chronic in around 60-80% of patients (Santantonio et al, 2008). Attention has focused on the envelope glycoproteins, E1 and E2, as key mediators of HCV entry. The two glycoproteins are major targets of neutralizing antibodies (Ball et al, 2014). A broadly-neutralizing antibody response contributes to clearance of acute infection (Dowd et al, 2008, Pestka et al, 2007, Raghuraman et al, 2012) and protection against reinfection (Osburn et al, 2010). Neutralizing activity of serum antibodies is inversely correlated with viral titer in acute HCV infection (Lavillette et al, 2005). Greater understanding of virus heterogeneity and entry will inform the design of drug entry inhibitors and vaccines for induction of broadly effective immunity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
