Early Evolution of the Human Immunodeficiency Virus Type 1 Subtype C Epidemic in Rural Malawi

McCormack, Grace P.; Glynn, Judith R.; Crampin, Amelia C.; Sibande, Felix; Mulawa, Dominic; Bliss, L.; Broadbent, Philip; Abarca, Katia; Pönnighaus, J. M.; Fine, Paul E. M.; Clewley, Jonathan P.

doi:10.1128/jvi.76.24.12890-12899.2002

Cited by 49 publications

(31 citation statements)

References 42 publications

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“…Regression analysis of four divergence estimates versus time suggested that the ancestor of this clade appeared between 1979 and 1981. This date is consistent with our previous conclusion, from molecular and epidemiological evidence, that a single individual may have been responsible for the introduction of this cluster shortly before 1983 (17). The good agreement between the methods and the plausible date produced give us a certain degree of confidence in the ability of these methods to estimate the most recent common ancestor of the larger data sets.…”

Section: Discussionsupporting

confidence: 78%

“…We applied our methods to the estimation of the most recent common ancestor of a well-described (17) clade within the subtype C phylogeny with gag sequences. Regression analysis of four divergence estimates versus time suggested that the ancestor of this clade appeared between 1979 and 1981.…”

Section: Discussionmentioning

confidence: 99%

“…Non-intersubtype-recombinant subtype C sequences spanning approximately 620 bp of the gag p17-p24 region and approximately 420 bp of the env C2-V3 region with known sampling dates were available from molecular epidemiological studies of HIV-1 in the Karonga District, Malawi (17). Only one member of each linked spouse pair was included.…”

Section: Methodsmentioning

confidence: 99%

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Timing and Reconstruction of the Most Recent Common Ancestor of the Subtype C Clade of Human Immunodeficiency Virus Type 1

Travers

Clewley

Glynn

et al. 2004

J Virol

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Human immunodeficiency virus type 1 (HIV-1) subtype C is responsible for more than 55% of HIV-1 infections worldwide. When this subtype first emerged is unknown. We have analyzed all available gag (p17 and p24) and env (C2-V3) subtype C sequences with known sampling dates, which ranged from 1983 to 2000. The majority of these sequences come from the Karonga District in Malawi and include some of the earliest known subtype C sequences. Linear regression analyses of sequence divergence estimates (with four different approaches) were plotted against sample year to estimate the year in which there was zero divergence from the reconstructed ancestral sequence. Here we suggest that the most recent common ancestor of subtype C appeared in the mid-to late 1960s. Sensitivity analyses, by which possible biases due to oversampling from one district were explored, gave very similar estimates.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

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Timing and Reconstruction of the Most Recent Common Ancestor of the Subtype C Clade of Human Immunodeficiency Virus Type 1

Travers

Clewley

Glynn

et al. 2004

J Virol

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“…Using additional data and analyses compared to previous reports, we were also able to further identify evidence of geographic clustering within the subtype C epidemic (11,16,30,33,34,37,40,43,45,51,57,58,62). Vaccine candidates designed on regional HIV-1 subtype C strains may be able to provide greater sequence coverage than those designed on all subtype C sequences detected to date.…”

Section: Discussionmentioning

confidence: 70%

Extensive Intrasubtype Recombination in South African Human Immunodeficiency Virus Type 1 Subtype C Infections

Rousseau

Learn

Bhattacharya

et al. 2007

J Virol

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Recombinant human immunodeficiency virus type 1 (HIV-1) strains containing sequences from different viral genetic subtypes (intersubtype) and different lineages from within the same subtype (intrasubtype) have been observed. A consequence of recombination can be the distortion of the phylogenetic signal. Several intersubtype recombinants have been identified; however, less is known about the frequency of intrasubtype recombination. For this study, near-full-length HIV-1 subtype C genomes from 270 individuals were evaluated for the presence of intrasubtype recombination. A sliding window schema (window, 2 kb; step, 385 bp) was used to partition the aligned sequences. The Shimodaira-Hasegawa test detected significant topological incongruence in 99.6% of the comparisons of the maximum-likelihood trees generated from each sequence partition, a result that could be explained by recombination. Using RECOMBINE, we detected significant levels of recombination using five random subsets of the sequences. With a set of 23 topologically consistent sequences used as references, bootscanning followed by the interactive informative site test defined recombination breakpoints. Using two multiple-comparison correction methods, 47% of the sequences showed significant evidence of recombination in both analyses. Estimated evolutionary rates were revised from 0.51%/year (95% confidence interval [CI], 0.39 to 0.53%) with all sequences to 0.46%/year (95% CI, 0.38 to 0.48%) with the putative recombinants removed. The timing of the subtype C epidemic origin was revised from 1961 (95% CI, 1947 to 1962) with all sequences to 1958 (95% CI, 1949 to 1960) with the putative recombinants removed. Thus, intrasubtype recombinants are common within the subtype C epidemic and these impact analyses of HIV-1 evolution.Human immunodeficiency virus type 1 (HIV-1) genetic diversity is generated during viral replication and is caused by error-prone reverse transcription, host-mediated hypermutation, and recombination. Recombination has been estimated to occur approximately 2.8 times per genome per viral replication cycle (61). Detectable recombination requires simultaneous infection with more than one virus at the cellular level. In a previous report, an average of three to four distinct proviral genomes were found in infected spleen cells (21), indicating that conditions do exist for extensive recombination between different viral genomes. Indeed, numerous intersubtype recombinants resulting in both unique forms found in single individuals and circulating forms have been observed (http://hiv-web.lanl.gov/content/hiv-db /CRFs/CRFs.html). Furthermore, recombination among sequences from the same subtype, or intrasubtype recombination, has also been observed within individual patients (36,47,59).Recombination can distort the phylogenetic signal. In phylogenetic analyses, the variant sites in the recombinant portions of the genome will appear as parallel evolution (homoplasy) instead of a single lineage. This can cause longer branch lengths, overestimate th...

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“…7 ART drugs were introduced in Malawi first in the context of prevention of maternal-to-child transmission (PMTCT) through antenatal clinics (using a mother and child nevirapine regime, which is ongoing). Full ART first became available at public clinics in the two major cities in Malawi in 2003, in the regional capital in 2004, and at Karonga district hospital in June 2005, at which time Karonga residents who had been seeking care outside the district were transferred to local services.…”

mentioning

confidence: 99%

Drug Resistance Mutations in Drug-Naive HIV Type 1 Subtype C-Infected Individuals from Rural Malawi

Bansode

Drebert

Travers

et al. 2011

AIDS Research and Human Retroviruses

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In this preliminary study we show that in 2008, 3 years after antiretroviral therapy was introduced into the Karonga District, Malawi, a greater than expected number of drug-naive individuals have been infected with HIV-1 subtype C virus harboring major and minor drug resistance mutations (DRMs). From a sample size of 40 reverse transcriptase (RT) consensus sequences from drug-naive individuals we found five showing NRTI and four showing NNRTI mutations with one individual showing both. From 29 protease consensus sequences, again from drug-naive individuals, we found evidence of minor DRMs in three. Additional major and minor DRMs were found in clonal sequences from a number of individuals that were not present in the original consensus sequences. This clearly illustrates the importance of sequencing multiple HIV-1 variants from individuals to fully assess drug resistance.

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Early Evolution of the Human Immunodeficiency Virus Type 1 Subtype C Epidemic in Rural Malawi

Cited by 49 publications

References 42 publications

Timing and Reconstruction of the Most Recent Common Ancestor of the Subtype C Clade of Human Immunodeficiency Virus Type 1

Timing and Reconstruction of the Most Recent Common Ancestor of the Subtype C Clade of Human Immunodeficiency Virus Type 1

Extensive Intrasubtype Recombination in South African Human Immunodeficiency Virus Type 1 Subtype C Infections

Drug Resistance Mutations in Drug-Naive HIV Type 1 Subtype C-Infected Individuals from Rural Malawi

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