Interferon Sensitivity Profiles of HIV-1 Transmitter Founder Viruses of Subtypes A, D and AD Recombinants in Uganda.

Abstract

ABSTRACT Background: In 80–90% of HIV-1 discordant partners, infection of the naive partner always results from the successful transmission and propagation of a single virus variant, termed the Transmitter Founder (TF) virus. These viruses might have unique properties that help their transmission and Targeting them maybe ideal to stop the transmission however, there is limited information on the resistance of HIV-1 Subtypes A, D and AD viruses to the effects of type-1 interferons (IFN-I). It is against this gap that this study aimed at determining resistance of the HIV-1 above subtypes to IFN-I (IFN- α & IFN-). Methodology: HIV-1 Infectious Molecular Clones were generated and transfected in 293 T cells. Peripheral blood mononuclear cells were infected with the generated viruses from 293 T cells in the presence of IFN- α & β at different concentrations. Supernatants from the cultures were sampled after every 48 hours for ten days. The replicative capacity (RC) were determined using the HIV-1 p24 antigen ELISA from which resistance to IFN-I were calculated. The transmission pair linkage and evolutionary divergence were determined using MEGA X software. Results: IFN-α was 1.2 folds more effective in inhibiting viral transmission than IFN- but this was independent of the varying amounts of the IFN-I used. The particle infectivity of the tested TF viruses positively correlated with their replicative capacities. Phylogenetic analysis showed that 7/8(87.5%) of transmission pairs analyzed were epidemiologically linked and the transmitted viruses are less evolved compared to the non-transmitted implying that evolution in the host decreases transmission potential hence transmission selection favoring Transmitted variants which are less evolved. Furthermore, the less evolved TF viruses had high particle infectivity. Subtype D was more resistant to the antiviral effect of IFN-α than subtype A among the TF variants tested while IFN- is less effective in inhibiting viral transmission. Future studies should focus at comparing the phenotypic properties of the viral transmission pairs for better understanding of the transmission potential of the TF variants regardless of the IFN-I inhibition effects. Key words: HIV-1 | Transmitter Founder viruses | Type 1 interferons Resistance | Evolutionary Divergence.