Anti-gp41 bNAbs have the potential to inhibit mDC-mediated HIV-1 infection because they bind plasma membranes prior to the formation of an infectious synapse, positioning them to neutralize subsequent virus transfer. As opposed to gp120-directed antibodies, anti-gp41 bNAbs might prevent HIV-1 infection if transmission or spread at the initial site of invasion occurs from a DC-associated source.

As HIV-1 evolves over the course of infection, resistance against antiretrovirals may arise in the absence of drug pressure, especially against receptor and fusion blockers because of the extensive changes observed in the envelope glycoprotein. Here we show that viruses from the chronic phase of disease are significantly less sensitive to CCR5 receptor and fusion blockers compared to early infection variants. Differences in susceptibility to CCR5 antagonists were observed in spite of no demonstrable CXCR4 receptor utilization. No significant sensitivity differences were observed to another entry blocker, soluble CD4, or to reverse transcriptase, protease, or integrase inhibitors. Chronic as compared to early phase variants demonstrated greater replication when passaged in the presence of subinhibitory concentrations of fusion but not CCR5 receptor inhibitors. Fusion antagonist resistance, however, emerged from only one chronic phase virus culture. Because sensitivity to receptor and fusion antagonists is correlated with receptor affinity and fusion capacity, respectively, changes that occur in the envelope glycoprotein over the course of infection confer greater ability to use the CCR5 receptor and increased fusion ability. Our in vitro passage studies suggest that these evolving phenotypes increase the likelihood of resistance against fusion but not CCR5 receptor blockers.

Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV) core region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg-positive/RNA-positive controls identified significant associations between the substitutions A48T and T49A/P and failure to detect HCVcAg (P < 0.05). Polymorphisms at residues 48 and 49 in the core protein are present across all major epidemic and endemic GTs. These findings have implications for HCV diagnosis, particularly in low-income regions in which GT3a HCV is endemic.

Recombination in Hepatitis C virus (HCV) is considered to be rare. In this study, we performed a phylogenetic analysis of 1278 full-length HCV genome sequences to identify potential recombination events. Nine inter-genotype recombinants were identified, all of which have been previously reported. This confirms the rarity of inter-genotype HCV recombinants. The analysis also identified five inter-subtype recombinants, four of which are documented for the first time (EU246930, EU246931, EU246932, and EU246937). Specifically, the latter represent four different novel recombination types (6a/6o, 6e/6o, 6e/6h, and 6n/6o), and this was well supported by seven independent methods embedded in RDP. The breakpoints of the four novel HCV recombinants are located within the NS5B coding region and were different from all previously reported breakpoints. While the locations of the breakpoints identified by RDP were not identical, they are very close. Our study suggests that while recombination in HCV is rare, this warrants further investigation.