Higher sequence diversity in the vaginal tract than in blood at early HIV-1 infection

Klein, Katja; Nickel, Gabrielle C.; Nankya, Immaculate; Kyeyune, Fred; Demers, Korey; Ndashimye, Emmanuel; Kwok, Cynthia; Chen, Pai Lien; Rwambuya, Sandra; Poon, Art F. Y.; Munjoma, Marshall; Chipato, Tsungai; Byamugisha, Josaphat; Mugyenyi, Peter; Salata, Robert A.; Morrison, Charles; Arts, Eric J.

doi:10.1371/journal.ppat.1006754

Cited by 16 publications

(20 citation statements)

References 57 publications

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“…Studies examining HIV‐1 diversity in the female genital tract during early infection have observed multiple variants not detected in the blood plasma . Multiple variants appear to be able to establish local foci of infection in the female genital tract, although perhaps only one or two are capable of initiating a disseminated infection.…”

Section: Discussionmentioning

confidence: 99%

Sexually transmitted infections and HIV in the era of antiretroviral treatment and prevention: the biologic basis for epidemiologic synergy

Cohen

Chen

2019

J Intern AIDS Soc

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Introduction HIV is a unique sexually transmitted infection (STI) that is greatly affected by other concomitant “classical” bacterial and viral STIs that cause genital ulcers and/or mucosal inflammation. STIs also serve as a marker for risky sexual behaviours. STIs increase infectiousness of people living with HIV by increasing the viral concentration in the genital tract, and by increasing the potential for HIV acquisition in people at risk for HIV. In addition, some STIs can increase blood HIV concentration and promote progression of disease. This review is designed to investigate the complex relationship between HIV and classical STIs. Discussion Treatment of STIs with appropriate antibiotics reduces HIV in blood, semen and female genital secretions. However, community‐based trials could not reliably reduce the spread of HIV by mass treatment of STIs. Introduction of antiretroviral agents for the treatment and prevention of HIV has led to renewed interest in the complex relationship between STIs and HIV. Antiretroviral treatment (ART) reduces the infectiousness of HIV and virtually eliminates the transmission of HIV in spite of concomitant or acquired STIs. However, while ART interrupts HIV transmission, it does not stop intermittent shedding of HIV in genital secretions. Such shedding of HIV is increased by STIs, although the viral copies are not likely replication competent or infectious. Pre‐exposure prophylaxis (PrEP) of HIV with the combination of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) prevents HIV acquisition in spite of concomitant STIs. Conclusions STIs remain pandemic, and the availability of ART may have led to an increase in STIs, as fear of HIV has diminished. Classical STIs present a huge worldwide health burden that cannot be separated from HIV, and they deserve far more attention than they currently receive.

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Section: Discussionmentioning

confidence: 99%

Sexually transmitted infections and HIV in the era of antiretroviral treatment and prevention: the biologic basis for epidemiologic synergy

Cohen

Chen

2019

J Intern AIDS Soc

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“…HIV-1 sequence diversity has been reported to be either higher (Klein et al, 2018) or similar (Piantadosi et al, 2019) to genital tract compared to blood. Viral compartmentalization between the blood and the male genital tract has been reported by multiple studies including SIV-infected macaques (Delwart et al, 1998;Paranjpe et al, 2002;Pillai et al, 2005;Coombs et al, 2006;Diem et al, 2008;Houzet et al, 2018).…”

Section: Hiv-1 Diversity Within the Latent And Reactivated Reservoirsmentioning

confidence: 99%

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Aït-Ammar

Kula

Darcis³

et al. 2020

Front. Microbiol.

119

123

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Quantitative polymerase chain reaction; QVOA, quantitative viral outgrowth assays; Rev, regulator of virion expression; RNA, ribonucleic acid; RNAPII, RNA polymerase II; RT-ddPCR, teverse transcription droplet digital PCR; SAHA, suberoylanilide hydroxamic acid; SIV, simian immunodeficiency virus; SMAC, second mitochondrial activator of caspases; SMYD2, SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing protein 2; Sp1, specificity protein 1; STAT5, signal transducer and activator of transcription 5; Suv39H1, Suppressor of variegation 3-9 homolog 1

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“…Studies focusing on the detection and characterization of viral populations in the female genital tract have proven difficult due to challenges in collecting genital tract samples and the generally low viral loads in this compartment (34,(55)(56)(57). We made use of CVL samples that were collected at multiple time points from women in the CAPRISA cohort enrolled during acute HIV-1 infection and monitored through to chronic infection (36).…”

Section: Discussionmentioning

confidence: 99%

“…A more recent study showed that there was higher HIV-1 Env sequence diversity in the vaginal tract early in infection than there was in the blood (34). This suggested the possibility of either restrictions in the movement of viruses from the genital tract to the systematic blood compartment or differences in HIV evolution within these respective compartments (34). However, this study utilized only the C2-V3-C3 region of Env and might have missed other tissue-specific signatures elsewhere in Env.…”

mentioning

confidence: 99%

“…However, investigations that used more advanced computational and statistical analyses failed to find evidence of compartmentalization and have suggested that such studies can be biased by monotypic and low-diversity sequences (32,33). A more recent study showed that there was higher HIV-1 Env sequence diversity in the vaginal tract early in infection than there was in the blood (34). This suggested the possibility of either restrictions in the movement of viruses from the genital tract to the systematic blood compartment or differences in HIV evolution within these respective compartments (34).…”

mentioning

confidence: 99%

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Evidence for both Intermittent and Persistent Compartmentalization of HIV-1 in the Female Genital Tract

Mabvakure

Lambson

Ramdayal

et al. 2019

J Virol

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HIV-1 has been shown to evolve independently in different anatomical compartments, but studies in the female genital tract have been inconclusive. Here, we examined evidence of compartmentalization using HIV-1 subtype C envelope (Env) glycoprotein genes (gp160) obtained from matched cervicovaginal lavage (CVL) and plasma samples over 2 to 3 years of infection. HIV-1 gp160 amplification from CVL was achieved for only 4 of 18 acutely infected women, and this was associated with the presence of proinflammatory cytokines and/or measurable viremia in the CVL. Maximum likelihood trees and divergence analyses showed that all four individuals had monophyletic compartment-specific clusters of CVL- and/or plasma-derived gp160 sequences at all or some time points. However, two participants (CAP177 and CAP217) had CVL gp160 diversity patterns that differed from those in plasma and showed restricted viral flow from the CVL. Statistical tests of compartmentalization revealed evidence of persistent compartment-specific gp160 evolution in CAP177, while in CAP217 this was intermittent. Lastly, we identified several Env sites that distinguished viruses in these two compartments; for CAP177, amino acid differences arose largely through positive selection, while insertions/deletions were more common in CAP217. In both cases these differences contributed to substantial charge changes spread across the Env. Our data indicate that, in some women, HIV-1 populations within the genital tract can have Env genetic features that differ from those of viruses in plasma, which could impact the sensitivity of viruses in the genital tract to vaginal microbicides and vaccine-elicited antibodies. IMPORTANCE Most HIV-1 infections in sub-Saharan Africa are acquired heterosexually through the genital mucosa. Understanding the properties of viruses replicating in the female genital tract, and whether these properties differ from those of more commonly studied viruses replicating in the blood, is therefore important. Using longitudinal CVL and plasma-derived sequences from four HIV-1 subtype C-infected women, we found fewer viral migrations from the genital tract to plasma than in the opposite direction, suggesting a mucosal sieve effect from the genital tract to the blood compartment. Evidence for both persistent and intermittent compartmentalization between the genital tract and plasma viruses during chronic infection was detected in two of four individuals, perhaps explaining previously conflicting findings. In cases where compartmentalization occurred, comparison of CVL- and plasma-derived HIV sequences indicated that distinct features of viral populations in the CVL may affect the efficacy of microbicides and vaccines designed to provide mucosal immunity.

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Higher sequence diversity in the vaginal tract than in blood at early HIV-1 infection

Cited by 16 publications

References 57 publications

Sexually transmitted infections and HIV in the era of antiretroviral treatment and prevention: the biologic basis for epidemiologic synergy

Sexually transmitted infections and HIV in the era of antiretroviral treatment and prevention: the biologic basis for epidemiologic synergy

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Evidence for both Intermittent and Persistent Compartmentalization of HIV-1 in the Female Genital Tract

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