Cryptic Multiple HIV-1 Infection Revealed by Early, Frequent, and Deep Sampling during Acute Infection

Hernan, KijakGustavo; Sanders-BuellEric,; ChenineAgnes-Laurance,; EllerMichael,; GoonetillekeNilu,; ThomasRasmi,; LeviyangSivan,; HarbolickElizabeth,; BoseMeera,; PhamPhuc,; OropezaCelina,; PoltaveeKultida,; Marie, O; MerbahMelanie,; CostanzoMargaret,; Lihui,; FischerWill,; Gaofeng,; Anne, EllerLeigh; O'ConnellRobert, J; SineiSamuel,; MagangaLucas,; KibuukaHannah,; NitayaphanSorachai,; RollandMorgane,; KorberBette,; McCutchanFrancine,; ShawGeorge,; MichaelNelson,; RobbMerlin,; TovanabutraSodsai,; KimJerome,

doi:10.1089/aid.2014.5102a.abstract

Cited by 4 publications

(7 citation statements)

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“…In this scenario, the virus with higher fitness would be successful and lower-fitness viruses would be lost. A prediction of this first scenario is that the multiple lineages that replicate initially at the site of transmission would occasionally give rise to viral recombinants, but deep sequencing viral populations during acute infection has not revealed recombinant genomes or rare genomes 94,95 (but see REF. 96).…”

Section: Transmission Bottlenecks In the Recipientmentioning

confidence: 99%

Bottlenecks in HIV-1 transmission: insights from the study of founder viruses

et al. 2015

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HIV-1 infection typically results from the transmission of a single viral variant, the transmitted/founder (T/F) virus. Studies of these HIV-1 variants provide critical information about the transmission bottlenecks and the selective pressures acting on the virus in the transmission fluid and in the recipient tissues. These studies reveal that T/F virus phenotypes are shaped by stochastic and selective forces that restrict transmission and may be targets for prevention strategies. In this Review, we highlight how studies of T/F viruses contribute to a better understanding of the biology of HIV-1 transmission and discuss how these findings affect HIV-1 prevention strategies.

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Section: Transmission Bottlenecks In the Recipientmentioning

confidence: 99%

Bottlenecks in HIV-1 transmission: insights from the study of founder viruses

et al. 2015

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“…Phylogenetic analyses of founder viruses in different epidemic settings support the notion of a genetic bottleneck with only a single founder in the large majority of heterosexual transmissions [ 14 – 16 ]. Moreover, founder viruses appear to be phenotypically distinct and specifically more resistant to IFN-α [ 15 , 17 , 18 ]. HIV transmission in MSM may have a higher proportion of multiple founders, which is thought to relate to a more permissive route of transmission [ 19 ].…”

Section: Early Events In Acute Hiv Infection and Relevance To Preventmentioning

confidence: 99%

“…It is not surprising that a more sensitive technique might find additional founders, and many of these additional founding viruses are closely related. Nevertheless, the importance of this finding accrues to the observation that these minor variants contribute to immune escape early in the course of HIV infection [ 18 ]. It will be critical to determine if minor variants have different phenotypes from the dominant founder and most importantly, if the diversity might limit HIV vaccine protection.…”

Section: Early Events In Acute Hiv Infection and Relevance To Preventmentioning

confidence: 99%

Lessons from acute HIV infection

Robb

Ananworanich

2016

Current Opinion in HIV and AIDS

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Purpose of reviewUnderstanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption).Recent findingsThe AHI period is brief and peak viremia predicts a viral set point that occurs 4–5 weeks following infection. Robust HIV-specific CD8+ T-cell responses lower viral set points. Phylogenetic analyses of founder viruses demonstrated unique bottleneck selections and specific genetic signatures to optimize for high-fitness variants and successful transmission events. HIV clades, route of transmission and the presence of minor variants may affect vaccine protection. Antiretroviral treatment in AHI results in smaller HIV reservoir size, better CD4+ T-cell recovery and fewer virus escapes.SummaryThe knowledge of untreated and treated AHI informs the development of vaccines, in that preventive vaccines will require broad coverage for multiple clades and antigenic variants associated with unique bottleneck selections. Vaccines that help the host to control viremia could minimize onward transmission. Therapeutic HIV vaccines aimed at HIV remission should be studied in early-treated individuals who have few or no viral escape mutants and a more preserved immune system.

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“…High-throughput sequencing (HTS) that produces massively parallel sequences is now being used to study complex genome populations (29)(30)(31)(32)(33). HTS provides improved resolution over Sanger sequencing for identification and analysis of heterogeneous viral subpopulations (31,34).…”

mentioning

confidence: 99%

“…Currently, HTS has been widely used to analyze viral quasispecies for small genomic regions (Ͻ500 bp). Minority variants present at Ն1% frequency in a sample can be characterized by HTS when sufficiently large numbers of templates are analyzed (33,43). However, when longrange PCR products (Ͼ4,000 bp) are analyzed, it is difficult to reliably identify subpopulations to understand the complexity of a quasispecies because short sequence reads cannot be reliably assembled into full-length consensus sequences for each subpopulation in the sample.…”

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confidence: 99%

Streamlined Subpopulation, Subtype, and Recombination Analysis of HIV-1 Half-Genome Sequences Generated by High-Throughput Sequencing

Hora

Gulzar

Chen

et al. 2020

mSphere

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High-throughput sequencing (HTS) has been widely used to characterize HIV-1 genome sequences. There are no algorithms currently that can directly determine genotype and quasispecies population using short HTS reads generated from long genome sequences without additional software. To establish a robust subpopulation, subtype, and recombination analysis workflow, we amplified the HIV-1 3′-half genome from plasma samples of 65 HIV-1-infected individuals and sequenced the entire amplicon (∼4,500 bp) by HTS. With direct analysis of raw reads using HIVE-hexahedron, we showed that 48% of samples harbored 2 to 13 subpopulations. We identified various subtypes (17 A1s, 4 Bs, 27 Cs, 6 CRF02_AGs, and 11 unique recombinant forms) and defined recombinant breakpoints of 10 recombinants. These results were validated with viral genome sequences generated by single genome sequencing (SGS) or the analysis of consensus sequence of the HTS reads. The HIVE-hexahedron workflow is more sensitive and accurate than just evaluating the consensus sequence and also more cost-effective than SGS. IMPORTANCE The highly recombinogenic nature of human immunodeficiency virus type 1 (HIV-1) leads to recombination and emergence of quasispecies. It is important to reliably identify subpopulations to understand the complexity of a viral population for drug resistance surveillance and vaccine development. High-throughput sequencing (HTS) provides improved resolution over Sanger sequencing for the analysis of heterogeneous viral subpopulations. However, current methods of analysis of HTS reads are unable to fully address accurate population reconstruction. Hence, there is a dire need for a more sensitive, accurate, user-friendly, and cost-effective method to analyze viral quasispecies. For this purpose, we have improved the HIVE-hexahedron algorithm that we previously developed with in silico short sequences to analyze raw HTS short reads. The significance of this study is that our standalone algorithm enables a streamlined analysis of quasispecies, subtype, and recombination patterns from long HIV-1 genome regions without the need of additional sequence analysis tools. Distinct viral populations and recombination patterns identified by HIVE-hexahedron are further validated by comparison with sequences obtained by single genome sequencing (SGS).

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Cryptic Multiple HIV-1 Infection Revealed by Early, Frequent, and Deep Sampling during Acute Infection

Cited by 4 publications

References 0 publications

Bottlenecks in HIV-1 transmission: insights from the study of founder viruses

Bottlenecks in HIV-1 transmission: insights from the study of founder viruses

Lessons from acute HIV infection

Streamlined Subpopulation, Subtype, and Recombination Analysis of HIV-1 Half-Genome Sequences Generated by High-Throughput Sequencing

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