Background: The demonstration of a virus population bottleneck at transmission and predominance of CCR5-using variants in acute infection raises the possibility that transmitted/founder (T/F) viruses might exhibit phenotypic properties that are uniquely or preferentially associated with transmission. We used single genome sequencing to generate infectious molecular clones of T/F (n=28) and chronic control (n=14) viruses of subtypes B (n=18) and C (n=24) and evaluated their biological properties.
Methods: The ability of T/F and chronic viruses to infect and replicate in CD4+ T cells was tested in the presence and absence of 500 U/ml IFN- and antibodies to 47. Virion infectivity and replication was evaluated in TZM-bl cells human lymphocytes and Env glycoprotein was quantified by an ELISA assay that used a CD4-induced antibody E51 linked to soluble CD4 to capture gp120. The ability of virus to bind to monocyte-derived dendritic cells (DCs) was also measured.
Results: T/F viruses replicated to slightly higher titers than chronic control viruses in CD4+ T cells (p=0.03). T/F viruses were significantly more resistant (10-fold) than chronic viruses to the inhibitory effects of INF- (p=0.008) but anti-47 had no effect. Virion-associated Env content and the per-particle infectivity assays revealed twice as much Env and two-fold greater infectivity of T/F viruses vs chronic control viruses (p=0.05 for both). T/F viruses were captured by DCs twice as efficiently as control viruses (p=0.03).
Conclusion: Compared with chronic control viruses, T/F viruses revealed higher Env content, higher infectivity, greater DC capture and relative resistance to IFN- but anti-47 had no effect on virus infection or replication
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