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

• Type of Material: Article
• Authors: Anne Kapaata, Medical Research Council, Uganda; Sheila N Balinda, Medical Research Council, Uganda; Rui Xu, Emory University; Maria G Salazar, Medical Research Council, Uganda; Kimberly Herard, Emory University; Kelsie Brooks, Emory University; Kato Laban, Medical Research Council, Uganda; Jonathan Hare, Imperial College London; Dario Dilernia, Emory University; Anatoli Kamali, IAVI, Nairobi Kenya; Eugene Ruzagira, Medical Research Council, Uganda; Freddie Mukasa, Medical Research Council, Uganda; Jill Gilmour, Imperial College London; Jesus F Salazar-Gonzalez, Medical Research Council, Uganda; Ling Yue, Emory University; Matthew Cotten, Medical Research Council, Uganda; Eric Hunter, Emory University; Pontiano Kaleebu, Medical Research Council, Uganda
• Language: English
• Date: 2021-02-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/v13020171
• Title of Journal or Parent Work: VIRUSES-BASEL
• Volume: 13
• Issue: 2
• Grant/Funding Information: This work was supported by IAVI and was made possible by generous support from many donors including the Bill and Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Department for International Development (DFID) and the United States Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org. The study was also supported in part by the Yerkes National primate research Centre base grant through the office of Research infrastructure programs/OD P51OD11132.
• Keywords: Science & Technology; HIV-1; Uganda; Life Sciences & Biomedicine; protein domains; recombinant; Virology; Gag-Pol
• Research Categories: Health Sciences, Public Health; Health Sciences, Health Care Management

Abstract

The ability to efficiently establish a new infection is a critical property for human immun-odeficiency 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.