Defining the human immunodeficiency virus type 1 transmission genetic bottleneck in a region with multiple circulating subtypes and recombinant forms

Nofemela, Andile; Bandawe, Gama; Ruwayhida, Thebus; Marais, Jinny C.; Wood, Natasha T.; Hoffmann, Oliver; Maboko, Leonard; Höelscher, Michael; Woodman, Zenda; Williamson, Carolyn

doi:10.1016/j.virol.2010.12.027

Cited by 10 publications

(7 citation statements)

References 22 publications

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“…URFs of HIV-1 with different recombination patterns have been reported previously in Tanzania [10], [16], [36], [38], [71]. No viral sequences closely related to the HIV-1 CRF10_CD reported previously in Tanzania [34], [37], [38] have been found in this study, suggesting no selective advantage of CRF10_CD in this population.…”

Section: Discussionsupporting

confidence: 47%

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HIV-1 Subtypes and Recombinants in Northern Tanzania: Distribution of Viral Quasispecies

et al. 2012

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This study analyzed the distribution and prevalence of HIV-1 subtypes, multiplicity of HIV-1 infection, and frequency of inter-subtype recombination among HIV-1-infected female bar and hotel workers in Moshi, Kilimanjaro Region, Tanzania, from 2004 to 2007. The HIV-1 viral sequences spanning the V1-C5 region of HIV-1 env gp120 were analyzed from 50 subjects by single genome amplification and sequencing (SGA/S) technique. A total of 1740 sequences were amplified and sequenced from the HIV-1 proviral DNA template. The median env sequences analyzed per subject per two time points was 38 (IQR 28–50) over one year of HIV infection. In a subset of 14 subjects, a total of 239 sequences were obtained from HIV-1 RNA template at the baseline visit. The most prevalent HIV-1 subtypes were A1 (56%) and C (30%), while HIV-1 subtype D and inter-subtype recombinant viruses were found in 6% and 8% of subjects respectively. Transmission of multiple HIV-1 variants was evident in 27% of the subjects infected with pure HIV-1 subtypes A1, C, or D. The HIV-1 inter-subtype recombinants were found in 8% including HIV-1 C/A, D/A, and complex mosaic recombinants. Multiple viral variants were found in two subjects infected with inter-subtype recombinants. One subject harbored quasispecies of both pure HIV-1 A1 and C/A recombinant. The other subject was infected with two complex mosaic inter-subtype recombinant variants belonging to subtype D. HIV-1 multiple infections and ongoing recombination contribute significantly to the genetic diversity of circulating HIV-1 in Tanzania and have important implications for vaccine design and the development of therapeutic strategies.

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Section: Discussionsupporting

confidence: 47%

“…The HIV-1 subtype profile was similar in the Mbeya region with the exception of subtype A2 and CRF10_CD which have not been found in the region [10]. Furthermore, HIV-1 multiple variants were reported in 23% of a high-risk population of female bar and hotel workers with acute HIV-1 infection in the Mbeya region of Tanzania [16].…”

Section: Introductionmentioning

confidence: 71%

HIV-1 Subtypes and Recombinants in Northern Tanzania: Distribution of Viral Quasispecies

et al. 2012

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“…Phusion High Fidelity polymerase was used for the second-round PCR with the primers ENV A (5¢-GCTTAG GCATCTCCTATGGCAGGAAGAA-3¢) and ENV N (5¢-CTGCCAATCAGGGAAGTAGCCTTGTGT-3¢). 8 The final PCR product (*3.2 kb) was ligated into the pcDNA3.1.V5-His TOPO TA vector according to the manufacturer's instructions (Invitrogen). Plasmid DNA was isolated from individual randomly picked white bacterial colonies and digested with the HindIII and NotI restriction enzymes (New England BioLabs) to screen for the presence of the insert.…”

Section: Introductionmentioning

confidence: 99%

Complex Subtype Diversity of HIV-1 Among Drug Users in Major Kenyan Cities

Gounder

Oyaro²,

Padayachi

et al. 2017

AIDS Research and Human Retroviruses

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Drug users are increasingly recognized as a key population driving human immunodeficiency virus (HIV) spread in sub-Saharan Africa. To determine HIV-1 subtypes circulating in this population group and explore possible geographic differences, we analyzed HIV-1 sequences among drug users from Nairobi, Mombasa, and Kisumu in Kenya. We sequenced gag and env from 55 drug users. Subtype analysis from 220 gag clonal sequences from 54 of 55 participants (median = 4/participant) showed that 44.4% were A, 16.7% were C, 3.7% were D, and 35.2% were intersubtype recombinants. Of 156 env clonal sequences from 48 of 55 subjects (median = 3/participant), 45.8% were subtype A, 14.6% were C, 6.3% were D, and 33.3% were recombinants. Comparative analysis of both genes showed that 30 (63.8%) participants had concordant subtypes, while 17 (36.2%) were discordant. We identified one genetically linked transmission pair and two cases of dual infection. These data are indicative of extensive HIV-1 intersubtype recombination in Kenya and suggest decline in subtype D prevalence.

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“…Functional Env clones were constructed from nine participants infected with either HIV-1 subtype C (n = 6) or recombinant CD (n = 2) or AD (n = 1) who were previously found to be infected with a single variant (Nofemela et al, 2011). All clones were identical to the consensus of the SGA-derived env amplicons, and assumed to represent the T/F virus responsible for clinical infection (Keele et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…Analysis of 212 Env sequences from 22 participants (n = 10 sequences per participant) generated using single genome amplification (SGA) indicated that sixteen participants were infected with a single infectious unit at transmission (Nofemela et al, 2011). Neighbour-joining trees and HIGHLIGHTER plots ( http://www.hiv.lanl.gov) of the SGA sequences were used to identify the sequence of the T/F virus, and the amplicons identical to the consensus sequence were cloned from nine acute stage participants as part of the Vaccine Immune Monitoring Consortium, Collaboration for AIDS Vaccine Discovery (VIMC -CAVD) (http://www.…”

Section: Cohort Descriptionmentioning

confidence: 99%

Phenotypic characterisation of Human Immunodeficiency Virus type 1 Envelope entry efficiency of transmitted/founder variants circulating in Mbeya, Tanzania

Woodman

Selhorst²,

Nofemela³

et al. 2015

MRAJ

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Background: Altered fitness of transmitted founder (T/F) HIV-1 variants has been linked to slowed disease progression, yet almost all of these studies have focussed on the role of attenuating immune escape mutations in T/F Gag or entry efficiency of Envelope (Env) in long-term non-progressors (LTNP) and elite suppressors (ES) during chronic stages of infection. As Env could also play an important role in viral fitness during early infection, we investigated if T/F Env entry efficiency, prior to immune selection, affected viral loads of progressors in vivo.

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Defining the human immunodeficiency virus type 1 transmission genetic bottleneck in a region with multiple circulating subtypes and recombinant forms

Cited by 10 publications

References 22 publications

HIV-1 Subtypes and Recombinants in Northern Tanzania: Distribution of Viral Quasispecies

HIV-1 Subtypes and Recombinants in Northern Tanzania: Distribution of Viral Quasispecies

Complex Subtype Diversity of HIV-1 Among Drug Users in Major Kenyan Cities

Phenotypic characterisation of Human Immunodeficiency Virus type 1 Envelope entry efficiency of transmitted/founder variants circulating in Mbeya, Tanzania

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