HIV-1 Gag-Pol Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity.

Anne Kapaata,Jonathan Hare,Jill Gilmour,Ling Yue,Matthew Cotten,Anatoli Kamali,Pontiano Kaleebu,Jesus F Salazar-Gonzalez,Dario Dilernia,Sheila N Balinda,Kato Laban,Maria G Salazar,Kelsie Brooks,Eugene Ruzagira,Kimberly Herard,Rui Xu,Freddie Mukasa,Eric Hunter

doi:10.3390/v13020171

Abstract

The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the Gag-Pol genes to replication capacity. A panel of Gag-Pol sequences generated using single genome amplification from incident HIV-1 infections were cloned into a common HIV-1 NL4.3 pol/env backbone and the influence of Gag-Pol changes on replication capacity was monitored. Using a novel protein domain approach, we then documented diversity in the functional protein domains across the Gag-Pol region and identified differences in the Gag-p6 domain that were frequently associated with higher in vitro replication.

Highlights

During early human immunodeficiency virus type 1 (HIV-1) infection, viremia increases rapidly, reaching a peak within weeks of infection, drops to a level that can remain stable over months to years of asymptomatic infection [1]
Thirty-two Ugandan protocol C participants had sequences successfully cloned from early samples drawn within 90 days of estimated date of HIV infection (EDI) and had their viral replicative capacity (VRC) characterized
We documented the VRC supported by Gag-Pol gene chimeras with

Summary

Introduction

During early HIV-1 infection, viremia increases rapidly, reaching a peak within weeks of infection, drops to a level (the set point viral load or SPVL) that can remain stable over months to years of asymptomatic infection [1]. High SPVL is a predictor of faster disease progression [2]. SPVL and viral control vary by infecting subtype, with subtype A associated with control [3,4]. Several studies report that the initial viruses establishing new HIV-1 infections may be important determinants of SPVL [12] and disease progression [13]. High viral replicative capacity (VRC) of transmitted HIV-1 among subtype C viruses has been associated with faster progression to disease [14,15].

Methods

Results

Conclusion