Phylogenetics of HIV-1 subtype G env: Greater complexity and older origins than previously reported

Tongo, Marcel; Essomba, René Ghislain; Nindo, Fredrick; Abrahams, Fatima; Nanfack, Aubin; Fokam, Joseph; Takou, Désiré; Torimiro, Judith; Mpoudi‐Ngolé, Eitel; Burgers, Wendy A.; Martin, Darren P.; Dorfman, Jeffrey R.

doi:10.1016/j.meegid.2015.07.017

Cited by 6 publications

(9 citation statements)

References 47 publications

(64 reference statements)

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“…In order to detect any bias inherent in the tree structure, we subjected each donor's tree sequences to a randomized tip swap (71,72), i.e., random assignment of sequences to compartment A or B in the same proportions as were present for the blood and semen compartments. None of the trees exhibited detectable compartmentalization after being subjected to this randomized tip swap, indicating that it is unlikely that positive scores were due to bias in the tree geometry (data not shown).…”

Section: Methodsmentioning

confidence: 99%

Compartmentalization and Clonal Amplification of HIV-1 in the Male Genital Tract Characterized Using Next-Generation Sequencing

Kariuki

Selhorst

Anthony

et al. 2020

J Virol

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Compartmentalization of HIV-1 between the systemic circulation and the male genital tract may have a substantial impact on which viruses are available for sexual transmission to new hosts. We studied compartmentalization and clonal amplification of HIV-1 populations between the blood and the genital tract from 10 antiretroviral-naive men using Illumina MiSeq with a PrimerID approach. We found evidence of some degree of compartmentalization in every study participant, unlike previous studies, which collectively showed that only ∼50% of analyzed individuals exhibited compartmentalization of HIV-1 lineages between the male genital tract (MGT) and blood. Using down-sampling simulations, we determined that this disparity can be explained by differences in sampling depth in that had we sequenced to a lower depth, we would also have found compartmentalization in only ∼50% of the study participants. For most study participants, phylogenetic trees were rooted in blood, suggesting that the male genital tract reservoir is seeded by incoming variants from the blood. Clonal amplification was observed in all study participants and was a characteristic of both blood and semen viral populations. We also show evidence for independent viral replication in the genital tract in the individual with the most severely compartmentalized HIV-1 populations. The degree of clonal amplification was not obviously associated with the extent of compartmentalization. We were also unable to detect any association between history of sexually transmitted infections and level of HIV-1 compartmentalization. Overall, our findings contribute to a better understanding of the dynamics that affect the composition of virus populations that are available for transmission. IMPORTANCE Within an individual living with HIV-1, factors that restrict the movement of HIV-1 between different compartments—such as between the blood and the male genital tract—could strongly influence which viruses reach sites in the body from which they can be transmitted. Using deep sequencing, we found strong evidence of restricted HIV-1 movements between the blood and genital tract in all 10 men that we studied. We additionally found that neither the degree to which particular genetic variants of HIV-1 proliferate (in blood or genital tract) nor an individual’s history of sexually transmitted infections detectably influenced the degree to which virus movements were restricted between the blood and genital tract. Last, we show evidence that viral replication gave rise to a large clonal amplification in semen in a donor with highly compartmentalized HIV-1 populations, raising the possibility that differential selection of HIV-1 variants in the genital tract may occur.

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Section: Methodsmentioning

confidence: 99%

Compartmentalization and Clonal Amplification of HIV-1 in the Male Genital Tract Characterized Using Next-Generation Sequencing

Kariuki

Selhorst

Anthony

et al. 2020

J Virol

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“…We first retrieved all full-length sequences belonging to the CRFs that were available within the Los Alamos National Laboratory HIV sequence database (LANL) ( LANL 2015 ) in October 2016. Because of the large numbers of sequences available for CRFs 01_AE and 02_AG, we selected representative sequences that included the broadest diversity within these clades ( Tongo et al. 2015b ).…”

Section: Methodsmentioning

confidence: 99%

“…The previously described viruses were queried against representatives of isolates from Subtypes A–H, J, and K. They were also queried against CRF01_AE, and CRF02_AG when they were isolated in individuals originating from countries within the Congo basin; and against CRF01_AE when viruses were sampled in South East Asia ( Tongo et al. 2015a , b ). For each recombinant, the reliability of plot topologies was assessed by bootstrapping with 500 replicates, and a sliding window of 450 bp advancing with 50-bp increments.…”

Section: Methodsmentioning

confidence: 99%

Patterns of genomic site inheritance in HIV-1M inter-subtype recombinants delineate the most likely genomic sites of subtype-specific adaptation

2018

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Recombination between different HIV-1 group M (HIV-1M) subtypes is a major contributor to the ongoing genetic diversification of HIV-1M. However, it remains unclear whether the different genome regions of recombinants are randomly inherited from the different subtypes. To elucidate this, we analysed the distribution within 82 circulating and 201 unique recombinant forms (CRFs/URFs), of genome fragments derived from HIV-1M Subtypes A, B, C, D, F, and G and CRF01_AE. We found that viruses belonging to the analysed HIV-1M subtypes and CRF01_AE contributed certain genome fragments more frequently during recombination than other fragments. Furthermore, we identified statistically significant hot-spots of Subtype A sequence inheritance in genomic regions encoding portions of Gag and Nef, Subtype B in Pol, Tat and Env, Subtype C in Vif, Subtype D in Pol and Env, Subtype F in Gag, Subtype G in Vpu-Env and Nef, and CRF01_AE inheritance in Vpu and Env. The apparent non-randomness in the frequencies with which different subtypes have contributed specific genome regions to known HIV-1M recombinants is consistent with selection strongly impacting the survival of inter-subtype recombinants. We propose that hotspots of genomic region inheritance are likely to demarcate the locations of subtype-specific adaptive genetic variations.

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“…Several studies have attempted to reconstruct the early dynamics of the different HIV-1M subtypes and other CRFs that are circulating in the CB [15,[27][28][29][30]. Using similar Bayesian statistical approaches, these studies have inferred that different lineages emerged at different locations in the region between the 1950s and 1970s and then spread out of the region.…”

Section: Diversification and Dissemination Of Hiv-1m Subtypesmentioning

confidence: 99%

“…Using similar Bayesian statistical approaches, these studies have inferred that different lineages emerged at different locations in the region between the 1950s and 1970s and then spread out of the region. For example, while subtype G likely originated from Cameroon in 1953 [27], the most recent common ancestors (MRCAs) of all the CRF01_AE and CRF02_AG viruses were, respectively located in the Central African Republic in 1970 [30] and the DRC [31] in 1973.…”

Section: Diversification and Dissemination Of Hiv-1m Subtypesmentioning

confidence: 99%

Elucidation of Early Evolution of HIV-1 Group M in the Congo Basin Using Computational Methods

Tongo

Martin

Dorfman

2021

Genes

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The Congo Basin region is believed to be the site of the cross-species transmission event that yielded HIV-1 group M (HIV-1M). It is thus likely that the virus has been present and evolving in the region since that cross-species transmission. As HIV-1M was only discovered in the early 1980s, our directly observed record of the epidemic is largely limited to the past four decades. Nevertheless, by exploiting the genetic relatedness of contemporary HIV-1M sequences, phylogenetic methods provide a powerful framework for investigating simultaneously the evolutionary and epidemiologic history of the virus. Such an approach has been taken to find that the currently classified HIV-1 M subtypes and Circulating Recombinant Forms (CRFs) do not give a complete view of HIV-1 diversity. In addition, the currently identified major HIV-1M subtypes were likely genetically predisposed to becoming a major component of the present epidemic, even before the events that resulted in the global epidemic. Further efforts have identified statistically significant hot- and cold-spots of HIV-1M subtypes sequence inheritance in genomic regions of recombinant forms. In this review we provide ours and others recent findings on the emergence and spread of HIV-1M variants in the region, which have provided insights into the early evolution of this virus.

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Phylogenetics of HIV-1 subtype G env: Greater complexity and older origins than previously reported

Cited by 6 publications

References 47 publications

Compartmentalization and Clonal Amplification of HIV-1 in the Male Genital Tract Characterized Using Next-Generation Sequencing

Compartmentalization and Clonal Amplification of HIV-1 in the Male Genital Tract Characterized Using Next-Generation Sequencing

Patterns of genomic site inheritance in HIV-1M inter-subtype recombinants delineate the most likely genomic sites of subtype-specific adaptation

Elucidation of Early Evolution of HIV-1 Group M in the Congo Basin Using Computational Methods

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