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. 2015 Oct;89(20):10688-92.
doi: 10.1128/JVI.01842-15. Epub 2015 Jul 29.

R5 Macrophage-Tropic HIV-1 in the Male Genital Tract

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Free PMC article

R5 Macrophage-Tropic HIV-1 in the Male Genital Tract

Maria M Bednar et al. J Virol. .
Free PMC article

Abstract

The entry tropism of HIV-1 Env proteins from virus isolated from the blood and genital tract of five men with compartmentalized lineages was determined. The Env proteins isolated from the genital tract of subject C018 were macrophage-tropic proteins, while the remaining cloned env genes encoded R5 T cell-tropic proteins. The detection of a macrophage-tropic lineage of HIV-1 within the male genital tract strongly suggests that evolution of macrophage-tropic viruses can occur in anatomically isolated sites outside the central nervous system.

Figures

FIG 1
FIG 1
Tissue culture assays using pseudoviruses to define viral entry tropism phenotypes. Relative levels of infectivity of pseudoviruses (represented by blue bars for seminal Env and red bars for plasma Env) were determined by using Affinofile cells expressing low levels of CD4 compared to the level of pseudovirus infection of Affinofile cells induced to express high levels of CD4. Macrophage tropism is defined by relative infectivity of greater than ∼10%, while T cell tropism is defined by relative infectivity of less than 2%. Relative infectivity from 2% to ∼10% constitutes intermediate tropism. Results show that only 1 Env from the semen of C018 showed macrophage tropism and that C047 and C083 had 1 intermediate-tropism Env from the semen whereas all other Env showed T cell-tropic phenotypes from both the blood and semen. BAL, BaL viral Env protein; JRCSF, viral Env protein; AID, amplicon identifier; PID, patient identifier.
FIG 2
FIG 2
Phylogenetic analysis of env sequences reveals compartmentalization between the blood and seminal plasma. A neighbor-joining tree, created using MEGA, of the sequences produced using SGA is shown. Filled blue triangles represent env sequences from seminal plasma, and filled red circles represent env sequences from blood plasma. The clustering of seminal plasma env sequences into separate lineages and results of previously described compartmentalization tests show distinct viral evolution within the male genital tract. Cloned and tropism-analyzed env sequences are marked with an asterisk (*) beside each label as indicated in the key.
FIG 3
FIG 3
Tissue culture assays using pseudoviruses to define viral entry tropism phenotypes. (A) Relative levels of infectivity of pseudoviruses (represented in blue bars for seminal Env and in red bars for plasma Env) were determined by using Affinofile cells expressing low levels of CD4 compared to the level of pseudovirus infection of Affinofile cells induced to express high levels of CD4. Macrophage tropism is defined by relative infectivity greater than 10%, while T cell tropism is defined by relative infectivity less than 2%. Relative infectivity from 2% to 10% constitutes intermediate tropism. Results show five macrophage-tropic Env from the semen, one intermediate-tropic Env from the semen, six T cell-tropic Env from the semen, and four T cell-tropic Env from the blood. (B) Relative levels of infectivity of TZM-bl cells (which express high levels of CD4 and CCR5) were compared in the presence and absence of sCD4. Near-complete entry inhibition by sCD4 identified five macrophage-tropic Env from semen, and these Env corresponded to those identified as macrophage-tropic by the Affinofile cell assay. Intermediate entry inhibition by sCD4 confirmed the intermediate tropism of one semen Env, and a lack of entry inhibition by sCD4 confirmed the T cell tropism of six Env from semen and four Env from the blood.

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