HIV diversity, molecular epidemiology, and the role of recombination

Kijak, Gustavo H.; McCutchan, Francine E.

doi:10.1007/s11908-005-0051-8

Cited by 48 publications

(36 citation statements)

References 51 publications

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“…A major obstacle for the development of a safe and globally effective HIV vaccine is the extensive genetic diversity of the virus (1,2). Most infections in the pandemic are due to HIV type 1 (HIV-1) group M, which is classified into nine subtypes (A to D, F to H, J, and K) differing by roughly 15% in their full-genome nucleotide sequence and up to 35% in the sequences of the gp120 envelope protein.…”

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confidence: 99%

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Kijak

Tovanabutra

Rerks-Ngarm

et al. 2013

J Virol

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The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results.

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Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Kijak

Tovanabutra

Rerks-Ngarm

et al. 2013

J Virol

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“…2 Multiple genotypes are involved in the HIV-1 epidemic (including A, B¢, B, C, CRF01_AE, CRF02_AG, CRF07_BC, CRF08_BC, and other unique recombinant forms). 3 Recombination between HIV-1 subtypes is a significant mechanism that contributes to the genetic complexity of HIV-1, and new strains are frequently found in regions and populations where multiple subtypes are circulating. One such region is Sichuan province in southwestern China.…”

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confidence: 99%

Near Full-Length Genomic Characterization of a Novel HIV Type 1 CRF07_ BC/01_AE Recombinant in Men Who Have Sex with Men from Sichuan, China

Wei

Feng

et al. 2013

AIDS Research and Human Retroviruses

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In recent years, the men who have sex with men (MSM) population has seen the fastest growing prevalence of HIV transmission in China. In addition, coinfection through sex and intravenous drug use is a major problem in HIV prevention and control. Recent studies have also revealed that three major viral strains (CRF07_BC, CRF01_AE, and subtype B) have been cocirculating among MSM in Sichuan, suggesting a high probability of generating new recombinants. This study reports a near full-length genome of a novel HIV-1 recombinant (MSM0720) between CRF07_BC and CRF01_AE. The analysis of MSM0720 shows that the genome is composed of at least 11 interlaced segments, including six CRF07_BC and five CRF01_AE segments, with CRF07_BC as the backbone; this is different from a previously identified CRF01_AE/07_BC recombinant strain in intravenous drug users from Jiangsu.

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“…This process allows viral recombination to occur between distantly related strains and may facilitate immune evasion (1,2), development of drug resistance (3), and disease progression (4)(5)(6). Moreover, new circulating recombinant forms complicate vaccine development by expanding global viral diversity (7,8). HIV-1 superinfection appears to occur more often early in infection and is associated with a weaker and immature immune response (9,10).…”

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Dynamics of Viral Evolution and Neutralizing Antibody Response after HIV-1 Superinfection

Chaillon

Wagner

Hepler

et al. 2013

J Virol

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e Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics in env following superinfection in a limited set of superinfection cases. HIV-1 env pyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination, and viral dynamics were evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to cocirculate. In the final individual, the surviving lineage was the product of interstrain recombination. NAb responses to autologous viruses that were detected within the first 2 years of HIV-1 infection were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in the env coding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination in env between initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers.

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HIV diversity, molecular epidemiology, and the role of recombination

Cited by 48 publications

References 51 publications

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Near Full-Length Genomic Characterization of a Novel HIV Type 1 CRF07_ BC/01_AE Recombinant in Men Who Have Sex with Men from Sichuan, China

Dynamics of Viral Evolution and Neutralizing Antibody Response after HIV-1 Superinfection

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