Monitoring HIV-1 Group M Subtypes in Yaoundé, Cameroon Reveals Broad Genetic Diversity and a Novel CRF02_AG/F2 Infection

Courtney, Colleen R.; Agyingi, Lucy; Fokou, Arlette; Christie, Stephanie; Asaah, Bladine; Meli, Josephine; Ngai, Johnson; Hewlett, Indira; Nyambi, Phillipe N.

doi:10.1089/aid.2015.0286

Cited by 20 publications

(27 citation statements)

References 13 publications

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“…They were shipped from the MDC under regulatory guidelines of transfer on biological samples to NYUSoM, where plasma was separated from peripheral blood mononuclear cells through Ficoll gradient centrifugation (Histopaque, Sigma‐Aldrich, St. Louis, MO, USA), and stored at −80°C. Eighteen URFs were selected based on previously published work from our group using partial genome sequencing (total of 509 participants) . Inclusion criteria were genetic evidence of URF infection and available plasma volumes ≥500 μL.…”

Section: Methodsmentioning

confidence: 99%

“…Possibly as a consequence, it has one of the most genetically diverse HIV epidemics in the world . The predominant lineage is the recombinant CRF02_AG, which accounts for more than half of infections . Also, circulating virus lineages include virtually every known HIV‐1 group M (HIV‐1 M) pure subtype, many CRFs, and a variety of URFs composed of pure, CRF and/or non‐classifiable sequences making this country a unique source of rare and emerging HIV‐1 M viral variants .…”

Section: Introductionmentioning

confidence: 99%

“…The predominant lineage is the recombinant CRF02_AG, which accounts for more than half of infections . Also, circulating virus lineages include virtually every known HIV‐1 group M (HIV‐1 M) pure subtype, many CRFs, and a variety of URFs composed of pure, CRF and/or non‐classifiable sequences making this country a unique source of rare and emerging HIV‐1 M viral variants . The range of subtypes and the extent of viral diversity within a geographical region considerably impact HIV diagnosis, treatment and prevention .…”

Section: Introductionmentioning

confidence: 99%

“…As part of our ongoing molecular surveillance efforts in Cameroon, our laboratories have in recent years identified and characterized two CRFs (CRF_36cpx and CRF_37cpx) , and we have monitored a steady increase in URFs . Through the application of a robust and versatile near full genome (NFG) amplification and sequencing technique , the current study characterized 18 near‐full genomes of HIV‐1 M recombinants.…”

Section: Introductionmentioning

confidence: 99%

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Near full genome characterization of HIV‐1 unique recombinant forms in Cameroon reveals dominant CRF02_AG and F2 recombination patterns

et al. 2019

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Introduction In Cameroon, a manifold diversity of HIV strains exists with CRF02_AG and unique recombinant forms (URFs) being the predominant strains. In recent years, a steady increase in URFs and clade F2 viruses has been monitored through partial genome sequencing. There is an information gap in the characterization of emerging URFs along the full genome, which is needed to address the challenges URFs pose towards diagnosis, treatment and HIV‐1 vaccine design. Method Eighteen Cameroonian URFs from samples collected between the years 2000 and 2015 were studied using a newly developed near full genome sequencing (NFGS) protocol based on variable nested RT‐PCRs with a versatile primer set. Near full genomes were characterized for recombination patterns and sequence signatures with possible impact on antiretroviral treatment or Env‐directed immune responses. Third‐generation sequencing (3GS) of near full or half genomes (HGs) gave insight into intra‐patient URF diversity. Results The characterized URFs were composed of a broad variety of subtypes and recombinants including A, F, G, CRF01_AE, CRF02_AG and CRF22_01A1. Phylogenetic analysis unveiled dominant CRF02_AG and F2 recombination patterns. 3GS indicated a high intra‐patient URF diversity with up to four distinct viral sub‐populations present in plasma at the same time. URF pol genomic analysis revealed a number of accessory drug resistance mutations (DRMs) in the ART‐naïve participants. Genotypic env analysis suggests CCR5 usage in 14/18 samples and identified deviations at residues, critical for gp120/gp41 interphase and CD4 binding site broadly neutralizing antibodies in more than half of the studied URFs. V1V2 sites of immune pressure in the human RV144 vaccine study varied in more than a third of URFs. Conclusions This study identified novel mosaic patterns in URFs in Cameroon. In line with the regional predominance of CRF_02AG and the increased prevalence of clade F2, prominent CRF_02AG and F2 background patterns were observed underlying the URFs. In the context of the novel mosaic genomes, the impact of the identified accessory DRMs and Env epitope variations on treatment and immune control remains elusive. The evolving diversity of HIV‐1 URFs in Cameroon requires continuous monitoring to respond to the increasing challenges for diagnosis, antiretroviral treatment and prevention.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Near full genome characterization of HIV‐1 unique recombinant forms in Cameroon reveals dominant CRF02_AG and F2 recombination patterns

et al. 2019

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“…Glycoprotein 120 from 12 plasma viruses (6 each from the V2-deficient and V2-reactive groups) was sequenced, and virus subtypes were identified (Table 1). All but one virus (clade C) were HIV-1 circulating recombinant forms (CRF), which dominate in Cameroon, according to recent analysis with the most prevalent CRF02_AG (64.9%) and CRF22_01A1 (7.1%) (11, 12). The identified subtypes in this study were as follows: CRF02_AG (3 plasma samples), CRF01_AE (2), CRF22_01A1 (2), CRF11_cpx, CRF18_cpx, CRF36_cpx, and CRF37_cpx (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Anti-V2 Antibody Deficiency in Individuals Infected With HIV-1

Liu

Nanfack

et al. 2018

Preprint

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25The positive correlation of high levels of plasma anti-V2 antibodies (Abs) with protective 26 immunity in the Phase III anti-HIV RV144 vaccine trial generated interest in the induction of 27 these Abs for HIV vaccine development. We analyzed plasma samples from 79 chronically 28 infected Cameroonian individuals for Ab reactivity against three V1V2 fusion proteins and five 29 cyclic V2 peptides and found that HIV-1 infection induces different levels of anti-V2 Abs. While 30 the majority of plasma samples reacted strongly with one or more V2 antigens, 10% (8) of the 31 samples were nonreactive. Deficiency of anti-V2 Abs was consistently found in longitudinal 32 plasma samples tested over 8 to 54 months of HIV infection. There was a strong correlation 33 between binding activities of plasma anti-V2 Abs and anti-gp120 and anti-gp41 Abs, suggesting 34 that deficiency of V2 Abs could be related, in part, to a limited ability to elicit strong Ab 35 responses. Analysis of gp120 sequences revealed that the V2 region of viruses from donors with 36 V2-deficient versus V2-reactive Abs displayed a tendency toward longer length, more glycans, 37 and lower isoelectric point and charge. No differences between these two patient groups were 38 noted in the same parameters measured in the V1 region. These data suggest that immunogens 39 containing a shorter V2 region with fewer glycosylation sites and higher electrostatic charges 40 would be beneficial for induction of anti-V2 Abs, but the ability to mount a strong general Ab 41 response to HIV-1 appears to be a dominant factor. 42IMPORTANCE The results of the RV144 vaccine clinical trial showed a correlation between 43 plasma Abs against a V1V2 fusion protein and a decreased risk of acquiring HIV-1 infection. 44This turned the focus of some HIV vaccine design to the induction of elevated levels of anti-V2 45Abs to increase vaccine efficacy. In plasma samples from Cameroonian individuals infected with 46 HIV-1, we observed broad variations in levels of anti-V2 Abs, and 8 of the 79 plasma samples 47 tested displayed substantial deficiency of V2 Abs. Sequence analysis of the V2 region from 48 plasma viruses and multivariate analyses of V2 characteristics showed a significant difference in 49 several features between V2-deficient and V2-reactive plasma Abs. These results suggest that 50 HIV vaccine immunogens containing a V2 region with shorter length, fewer glycosylation sites, 51 and higher electrostatic charges may be beneficial for induction of a higher level of anti-V2 Abs 52 and thus contribute to HIV vaccine efficacy. 53 54 KEYWORDS HIV-1, V1V2 region, V2 conformational antibodies, V2 linear antibodies, V2 55 antibody deficiency 56 57 4Anti-V2 antibodies (Abs) have been the subject of studies to determine their role in 58 protection against HIV-1 infection due to the results of the Phase III RV144 vaccine trial, which 59 showed an inverse correlation with risk of infection (1). The RV144 data revealed that the V2 60 Abs in vaccinees were highly cross-clade reactive and tha...

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Monitoring HIV-1 Group M Subtypes in Yaoundé, Cameroon Reveals Broad Genetic Diversity and a Novel CRF02_AG/F2 Infection

Cited by 20 publications

References 13 publications

Near full genome characterization of HIV‐1 unique recombinant forms in Cameroon reveals dominant CRF02_AG and F2 recombination patterns

Near full genome characterization of HIV‐1 unique recombinant forms in Cameroon reveals dominant CRF02_AG and F2 recombination patterns

Anti-V2 Antibody Deficiency in Individuals Infected With HIV-1

Detection of highly divergent HIV‐1 in clinical specimens using rapid HIV serologic assays

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