The Human Immunodeficiency Virus Type 1 Envelope Confers Higher Rates of Replicative Fitness to Perinatally Transmitted Viruses than to Nontransmitted Viruses

Authors

Xiaohong Kong, University of Nebraska-Lincoln
John T. West, University of Nebraska-LincolnFollow
Hong Zhang, University of Nebraska-Lincoln
Danielle M. Shea, University of Nebraska-LincolnFollow
Tendai J. M’soka, University Teaching Hospital, Lusaka
Charles Wood, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2008

Citation

Journal of Virology, Dec. 2008, p. 11609–11618

Comments

Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Abstract

Selection of a minor viral genotype during perinatal transmission of human Immunodeficiency virus type 1

(HIV-1) has been observed, but there is a lack of information on the correlation of the restrictive transmission

with biological properties of the virus, such as replicative fitness. Recombinant viruses expressing the enhanced

green fluorescent protein or the Discosoma sp. red fluorescent (DsRed2) protein carrying the V1 to V5

regions of env from seven mother-infant pairs (MIPs) infected by subtype C HIV-1 were constructed, and

competition assays were carried out to compare the fitness between the transmitted and nontransmitted

viruses. Flow cytometry was used to quantify the frequency of infected cells, and the replicative fitness was

determined based on a calculation that takes into account replication of competing viruses in a single infection

versus dual infections. Transmitted viruses from five MIPs with the mothers chronically infected showed a

restrictive env genotype, and all the recombinant viruses carrying the infants’ Env had higher replicative fitness

than those carrying the Env from the mothers. This growth fitness is lineage specific and can be observed only

within the same MIP. In contrast, in two MIPs where the mothers had undergone recent acute infection, the

viral Env sequences were similar between the mothers and infants and showed no further restriction in

quasispecies during perinatal transmission. The recombinant viruses carrying the Env from the infants’

viruses also showed replication fitness similar to those carrying the mothers’ Env proteins. Our results suggest

that newly transmitted viruses from chronically infected mothers have been selected to have higher replicative

fitness to favor transmission, and this advantage is conferred by the V1 to V5 region of Env of the transmitted

viruses. This finding has important implications for vaccine design or development of strategies to prevent

HIV-1 transmission.