Abstract
Heterosexual HIV-1 transmission has been identified as a genetic bottleneck and a single transmitted/founder (T/F) variant with reduced sensitivity to type I interferon initiates productive infection in most cases. We hypothesized that particularly active accessory protein(s) may confer T/F viruses with a selective advantage in establishing HIV infection. Thus, we tested vpu, vif and nef alleles from six T/F and six chronic (CC) viruses in assays for 9 immune evasion activities involving the counteraction of interferon-stimulated genes and modulation of ligands known to activate innate immune cells. All functions were highly conserved with no significant differences between T/F and CC viruses, suggesting that these accessory protein functions are important throughout the course of infection.
Highlights
Studies have defined a genetic ‘bottleneck’ at mucosal HIV-1 transmission with a single inferred variant initiating peripheral viremia in most cases (Baalwa et al, 2013; Fenton-May et al, 2013; Haaland et al, 2009; Ochsenbauer et al, 2012; Parrish et al, 2013; Salazar-Gonzalez et al, 2009)
In particular it has been noted that transmitted founder (T/F) Envelope proteins are R5 tropic with both increased sensitivity to broadly neutralizing antibodies (Wilen et al, 2011) and reduced ability to interact with maraviroc-bound CCR5 compared to viruses isolated from chronic infection (Parker et al, 2013)
It has been reported that T/F viruses are less restricted by interferon (IFN) in primary T cells than chronic controls (Fenton-May et al, 2013; Parrish et al, 2013)
Summary
Studies have defined a genetic ‘bottleneck’ at mucosal HIV-1 transmission with a single inferred variant initiating peripheral viremia in most cases (Baalwa et al, 2013; Fenton-May et al, 2013; Haaland et al, 2009; Ochsenbauer et al, 2012; Parrish et al, 2013; Salazar-Gonzalez et al, 2009). In particular it has been noted that transmitted founder (T/F) Envelope proteins are R5 tropic with both increased sensitivity to broadly neutralizing antibodies (Wilen et al, 2011) and reduced ability to interact with maraviroc-bound CCR5 compared to viruses isolated from chronic infection (Parker et al, 2013). It has been reported that T/F viruses are less restricted by interferon (IFN) in primary T cells than chronic controls (Fenton-May et al, 2013; Parrish et al, 2013).
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