Sexually-Transmitted/Founder HIV-1 Cannot Be Directly Predicted from Plasma or PBMC-Derived Viral Quasispecies in the Transmitting Partner

Frange, Pierre; Meyer, Laurence; Jung, Matthieu; Goujard, Cécile; Zucman, David; Abel, Sylvie; Hochedez, Patrick; Gousset, Marine; Gascuel, Olivier; Rouzioux, Christine; Chaix, Marie‐Laure

doi:10.1371/journal.pone.0069144

Cited by 18 publications

(17 citation statements)

References 48 publications

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“…The assumption of direct transmission of the mixed variants in subject 10BR_023RJ do not support the hypothesis of gatekeeping event that almost always selects for transmission of R5 over ×4 HIV-1 strains [ 44 ]. Indeed, there is no convincing evidence has yet been published to proof the lower transmissibility of ×4 viruses but available data support the idea that R5 or D/M infections could result from a stochastic process [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected blood donors by massively parallel sequencing: the REDS II study

Pessôa

Sabino

Sanabani

2015

Virol J

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BackgroundThe interaction of HIV-1 and target cells involves sequential binding of the viral gp120 Env protein to the CD4 receptor and a chemokine co-receptor (either CCR5 or CXCR4). CCR5 antagonists have proved to be an effective salvage therapy in patients with CCR5 using variants (R5) but not with variants capable of using CXCR4 (×4) phenotype. Thus, it is critically important to determine cellular tropism of a country’s circulating HIV strains to guide a management decision to improve treatment outcome. In this study, we report the prevalence of R5 and ×4 HIV strains in 45 proviral DNA massively parallel sequencing “MPS” data from recently infected Brazilian blood donors.MethodsThe MPS data encompassing the tropism-related V3 loop region of the HIV‐1 env gene was extracted from our recently published HIV-1 genomes sequenced by a paired-end protocol (Illumina). HIV‐1 tropism was inferred using Geno2pheno[coreceptor] algorithm (3.5 % false-positive rate). V3 net charge and 11/25 rules were also used for coreceptor prediction.ResultsAmong the 45 samples for which tropism were determined, 39 were exclusively R5 variants, 5 ×4 variants, and one dual-tropic or mixed (D/M) populations of R5 and ×4 viruses, corresponding to 86.7, 11.1 and 2.2 %, respectively. Thus, the proportion of all blood donors that harbor CXCR4-using virus was 13.3 % including individuals with D/M-tropic viruses.ConclusionsThe presence of CCR5-tropic variants in more than 85 % of our cohort of antiretroviral-naïve blood donors with recent HIV-1 infection indicates a potential benefit of CCR5 antagonists as a therapeutic option in Brazil. Therefore, determination of viral co-receptor tropism is an important diagnostic prerequisite.

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Section: Discussionmentioning

confidence: 99%

Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected blood donors by massively parallel sequencing: the REDS II study

Pessôa

Sabino

Sanabani

2015

Virol J

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“…However, neither study identified associations with particular STIs; they only observed associations with any vaginal/urethral discharges in the recipients [5] or when grouping together occurrences of a number of STIs [90]. Other studies were unable to observe this association [92, 93]. It is possible that these latter studies were underpowered to detect the association; perhaps they failed to have a sufficient number of cases of the particular STIs most responsible for the observed increased risk of multivariant transmission.…”

Section: Sexually Transmitted Infections and Risk Of Multivariant Tramentioning

confidence: 99%

“…In order to study selection of the transmitted virus in detail, samples are taken from the donor blood as well as from the recipient blood. This is followed by subcloning and bulk sequencing [194, 195], single genome amplification (SGA)-based analysis [6–8, 93] or deep sequencing-based analysis [196]. Earlier studies of the T/F virus relied on collecting the sample material a few months following appearance of infection symptoms followed by bulk PCR-based methods, cloning, sequencing and phylogenetic analysis [27, 105, 110, 194, 197, 198] or heteroduplex tracking assay (HTA) [194, 197, 198].…”

Section: Impact Of Approaches Used To Study the Transmitted Virus Upomentioning

confidence: 99%

The HIV-1 transmission bottleneck

et al. 2017

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It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient’s genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor’s general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient’s genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient.

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“…The loose association between viral phenotypes and improved transmission was also demonstrated by a study of molecular infectious clone [9]. In the absence of clear differences in infectivity, there is little hope for predicting which variant(s) in the donor will become the founder strain(s) in a new infection [10]. …”

Section: Introductionmentioning

confidence: 99%

Disentangling the impact of within-host evolution and transmission dynamics on the tempo of HIV-1 evolution

Vrancken

Baele

Vandamme

et al. 2015

Aids

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Background Although evidence exists for a selective component at transmission, it is clear that HIV-1 transmission is also to a large extent driven by drift. The variation in inoculum size among different risk groups therefore implies that the adaptation rate of HIV may vary between epidemics with different risk group compositions. Furthermore, factors that govern the rate of within-host evolution may also vary by risk group and therefore contribute to evolutionary differences at the epidemic level. Methods We adopted a population genetic approach to test whether the different proportions of multi-variant transmissions are reflected by varying proportions of transmitted diversity between men-having-sex-with-men (MSM), heterosexual (HET) and direct blood contact (BC) sub-populations. To this purpose, we collected all available transmission chain clonal sequence data sets (n = 70) available at the Los Alamos HIV website and through an extensive literature search. To assess evolutionary rate differences among different risk groups, we compiled risk group datasets for several subtypes and directly compared the absolute substitution rate and its synonymous and non-synonymous components. Results There was sufficient demographic signal to inform the transmission model in BEAST using env data to compare the transmission bottleneck size between the MSM and HET risk groups, i.e. the largest contributors to HIV spread. We find no indications for a different proportion of transmitted genetic diversity at the population level between these groups. In the direct rate comparisons between risk groups, however, we consistently recover a higher evolutionary rate in the male dominated risk group compared to the HET datasets. Conclusions We find that the risk group composition impacts the viral evolutionary rate and therefore potentially also the adaptation rate. In particular, risk group-specific sex ratios, and the variation in within-host evolutionary rates between males and females, imposes evolutionary rate differences at the epidemic level, but we cannot exclude a role of varying transmission rates.

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Sexually-Transmitted/Founder HIV-1 Cannot Be Directly Predicted from Plasma or PBMC-Derived Viral Quasispecies in the Transmitting Partner

Cited by 18 publications

References 48 publications

Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected blood donors by massively parallel sequencing: the REDS II study

Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected blood donors by massively parallel sequencing: the REDS II study

The HIV-1 transmission bottleneck

Disentangling the impact of within-host evolution and transmission dynamics on the tempo of HIV-1 evolution

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