Genital Tract Human Immunodeficiency Virus Type 1 (HIV‐1) Shedding and Inflammation and HIV‐1<i>env</i>Diversity in Perinatal HIV‐1 Transmission

Previous studies have provided conflicting data on the presence of selective pressures in the transmission of a homogeneous maternal viral subpopulation to the infant. Therefore, the purpose of this study was to definitively characterize the human immunodeficiency virus type 1 (HIV-1) quasispecies transmitted in utero and intrapartum. HIV-1 envelope gene diversity from peripheral blood mononuclear cells and plasma was measured during gestation and at delivery in mothers who did and did not transmit HIV perinatally by using a DNA heteroduplex mobility assay. Children were defined as infected in utero or intrapartum based on the timing of the first detection of HIV. Untreated transmitting mothers (n ‫؍‬ 19) had significantly lower HIV-1 quasispecies diversity at delivery than untreated nontransmittting mothers (n ‫؍‬ 18

Section: Discussionmentioning

confidence: 99%

Perinatal Transmission of Major, Minor, and Multiple Maternal Human Immunodeficiency Virus Type 1 Variants In Utero and Intrapartum

Dickover

Garratty

Plaeger

et al. 2001

“…Furthermore, maternal genital secretions are believed to contain virus that can be perinatally transmitted to infants during a vaginal delivery (9). The report of an association between greater cell-free HIV-1 diversity in VS with perinatal transmission (45) shows that evaluations of viral quasispecies dynamics in genital secretions are necessary components for determining the viral and host-related mechanisms of transmission. The data from our study should help in interpreting how future immune and vaccine therapies could impact the natural course of HIV-1 shed in VS and how these changes are associated with a woman's immune status.…”

Section: Vol 79 2005 Hiv Quasispecies Shed In the Female Genital Trmentioning

confidence: 99%

Diversity, Divergence, and Evolution of Cell-Free Human Immunodeficiency Virus Type 1 in Vaginal Secretions and Blood of Chronically Infected Women: Associations with Immune Status

Sullivan

Mandava

Evans-Strickfaden

et al. 2005

Most human immunodeficiency virus type 1 (HIV-1) infections are believed to be the result of exposure to the virus in genital secretions. However, prevention and therapeutic strategies are usually based on characterizations of HIV-1 in blood. To understand better the dynamics between HIV-1 quasispecies in the genital tract and blood, we performed heteroduplex assays on amplified env products from cell-free viral RNA in paired vaginal secretion (VS) and blood plasma (BP) samples of 14 women followed for 1.5 to 3.5 years. Diversity and divergence were less in VS than in BP (P ‫؍‬ 0.03 and P < 0.01, respectively), and divergence at both sites was correlated with blood CD4 ؉ cell levels (VS, P ‫؍‬ 0.05; BP, P ‫؍‬ 0.01). Evolution of quasispecies was observed in 58% of the women; the loss or gain of quasispecies in VS or BP was always accompanied by such changes at the other site. In addition, sustained compartmentalization of quasispecies in VS was found for four women, even as CD4 ؉ cell levels decreased to low levels (<50 cells/l). Quasispecies changes over time were associated with fluctuations in CD4 ؉ cell levels; concordant increases or decreases in VS and BP divergence had greater CD4 ؉ cell level changes than intervals with discordant changes (P ‫؍‬ 0.05), and women with evolving quasispecies had greater decreases in CD4؉ cell levels compared to that for women who maintained the same quasispecies (P < 0.05). Thus, diversity, divergence, and evolution of cell-free HIV-1 in VS can be different from that in BP, and dynamics between their respective quasispecies are associated with changes in CD4 ؉ cell levels.

“…Since viral replication and therefore genotypic evolution are driven by the inflammatory state of the infected cell, the dynamic inflammatory environment of the gastrointestinal mucosa may drive viral evolution to a greater extent than is seen in the peripheral blood compartment (41). Enhanced viral evolution at an inflamed mucosal site was suggested by Panther et al, who showed greater env heterogeneity in the female genital tract compared to paired blood samples (33). A number of other studies examining lymphoid and nonlymphoid tissue compartments have also suggested compartmentalization of viral evolution (9,15,20,21,22,30,51).…”

Section: Ccr5mentioning

confidence: 99%

A Preponderance of CCR5⁺CXCR4⁺Mononuclear Cells Enhances Gastrointestinal Mucosal Susceptibility to Human Immunodeficiency Virus Type 1 Infection

Poles¹,

Elliott²,

Taing³

et al. 2001

153

106

The gastrointestinal mucosa harbors the majority of the body's CD4؉ cells and appears to be uniquely susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We undertook this study to examine the role of differences in chemokine receptor expression on infection of mucosal mononuclear cells ( , while these cells make up less than 20% of the peripheral blood cells. It is this cell population that is most susceptible to infection with both R5-and X4-tropic HIV-1 in both compartments. Regardless of whether viral isolates were derived from the blood or mucosa of HIV-1-infected patients, HIV-1 p24 production was greater in MMCs than in PBMCs. Further, the chemokine receptor tropism of these patient-derived viral isolates did not differ between compartments. We conclude that, based on these findings, the gastrointestinal mucosa represents a favored target for HIV-1, in part due to its large population of CXCR4 ؉ CCR5 ؉ target cells and not to differences in the virus that it contains.