Multiple-infection and recombination in HIV-1 within a longitudinal cohort of women

Templeton, Alan R.; Kramer, Melissa G.; Jarvis, Joseph P.; Kowalski, Jeanne; Gange, Stephen J.; Schneider, Michael; Shao, Qiujia; Zhang, Guang Wen; Yeh, Mei Fen; Tsai, Hua Ling; Zhang, Hong; Markham, Richard B.

doi:10.1186/1742-4690-6-54

Cited by 38 publications

(40 citation statements)

References 35 publications

(65 reference statements)

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“…We sequenced 30 viruses from each of the Thai individuals having B-clade infections and found no traces of CRF01 coinfection; however, CRF01 may have been present at levels too low to detect by this method. Also, transiently detected superinfections have been reported (97,98). Alternatively, host factors, whether genetic or environmental (e.g., exposure to an HIV-1 cross-reactive epitope from an organism in the Thai communities where the samples were obtained), might explain the shared serological profiles (84).…”

Section: Discussionmentioning

confidence: 99%

Impact of Clade, Geography, and Age of the Epidemic on HIV-1 Neutralization by Antibodies

Hraber

Korber

Lapedes

et al. 2014

J Virol

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Neutralizing antibodies (nAbs) are a high priority for vaccines that aim to prevent the acquisition of HIV-1 infection. Vaccine effectiveness will depend on the extent to which induced antibodies neutralize the global diversity of circulating HIV-1 variants. Using large panels of genetically and geographically diverse HIV-1 Env-pseudotyped viruses and chronic infection plasma samples, we unambiguously show that cross-clade nAb responses are commonly induced in response to infection by any virus clade. Nonetheless, neutralization was significantly greater when the plasma clade matched the clade of the virus being tested. This within-clade advantage was diminished in older, more-diverse epidemics in southern Africa, the United States, and Europe compared to more recent epidemics in Asia. It was most pronounced for circulating recombinant form (CRF) 07_BC, which is common in China and is the least-divergent lineage studied; this was followed by the slightly more diverse Asian CRF01_AE. We found no evidence that transmitted/founder viruses are generally more susceptible to neutralization and are therefore easier targets for vaccination than chronic viruses. Features of the gp120 V1V2 loop, in particular, length, net charge, and number of N-linked glycans, were associated with Env susceptibility and plasma neutralization potency in a manner consistent with neutralization escape being a force that drives viral diversification and plasma neutralization breadth. The overall susceptibility of Envs and potencies of plasma samples were highly predictive of the neutralization outcome of any single virus-plasma combination. These findings highlight important considerations for the design and testing of candidate HIV-1 vaccines that aim to elicit effective nAbs. IMPORTANCEAn effective HIV-1 vaccine will need to overcome the extraordinary variability of the virus, which is most pronounced in the envelope glycoproteins (Env), which are the sole targets for neutralizing antibodies (nAbs). Distinct genetic lineages, or clades, of HIV-1 occur in different locales that may require special consideration when designing and testing vaccines candidates. We show that nAb responses to HIV-1 infection are generally active across clades but are most potent within clades. Because effective vaccine-induced nAbs are likely to share these properties, optimal coverage of a particular clade or combination of clades may require clade-matched immunogens. Optimal within-clade coverage might be easier to achieve in regions such as China and Thailand, where the epidemic is more recent and the virus less diverse than in southern Africa, the United States, and Europe. Finally, features of the first and second hypervariable regions of gp120 (V1V2) may be critical for optimal vaccine design.

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Section: Discussionmentioning

confidence: 99%

Impact of Clade, Geography, and Age of the Epidemic on HIV-1 Neutralization by Antibodies

Hraber

Korber

Lapedes

et al. 2014

J Virol

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“…1 This analysis examined the protease-RT region of pol and the C2V5 region of env amplified from two to four samples from 58 women at 6-to 24-month intervals, and showed findings similar to the present study with regard to temporal fluctuation of the dually infecting strains, in that of the 18 cases in which dual infection was identified at a single interim time point, 16 found no evidence of the second strain in subsequent samples, and in three cases, the initial strain was almost overtaken by the second strain. Furthermore, it was found that among the 31% who were dually infected, recombination had occurred between the pol and env loci in nearly all individuals, and recombination within the loci studied had occurred in three individuals.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9] Among such studies includes one published by Baird et al, which examined the C1C4 region of env for recombination between two discordant HIV-1 subtypes, A and D, in cell culture demonstrating an abundance of recombinants and revealing recombination breakpoints occurring more frequently in the constant than in the variable regions of the viral envelope. 8 Subsequent in vitro studies with these discordant strains also revealed that factors such as replicative fitness contribute to the frequency at which two viral strains recombine.…”

mentioning

confidence: 99%

Longitudinal Quasispecies Analysis of Viral Variants in HIV Type 1 Dually Infected Individuals Highlights the Importance of Sequence Identity in Viral Recombination

Powell

Lezeau²,

Kinge³

et al. 2010

AIDS Research and Human Retroviruses

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Little is known regarding the likelihood of recombination between any given pair of nonidentical HIV-1 viruses in vivo. The present study analyzes the HIV-1 quasispecies in the C1C2 region of env, the vif-vpr-vpu accessory gene region, and the reverse transcriptase region of pol. These sequences were amplified from samples obtained sequentially over a 12-to 33-month period from five dually HIV-1-infected subjects. Analysis of an average of 248 clones amplified from each subject revealed no recombinants within the three loci studied of the subtypediscordant infecting strains, whose genetic diversity was >11% in env. In contrast, two subjects who were initially coinfected by two subtype-concordant variants with genetic diversity of 7.4% in env were found to harbor 10 unique recombinants of these strains, as exhibited by analysis of the env gene. The frequent recombination observed among the subtype-concordant strains studied herein correlates with prior sequence analyses that have commonly found higher rates of recombination at loci bearing the most conserved sequences, demonstrating an important role for sequence identity in HIV-1 recombination. Viral load analysis revealed that the samples studied contained an average of 8125 virus copies=ml (range, 882-31,626 copies=ml), signifying that the amount of viral RNA in the samples was not limiting for studying virus diversity. These data reveal that recombination between genetically distant strains may not be an immediate or common outcome to dual infection in vivo and suggest critical roles for viral and host factors such as viral fitness, virus diversity, and host immune responses that may contribute to limiting the frequency of intersubtype recombination during in vivo dual infection.

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“…Pol sequencing alone, which is easily available as part of the routine testing for drug resistance mutations of treated patients, can be used as a second tool to screen for HIV-1 superinfection, which might be associated with consequent changes in the pol sequence and/or treatment susceptibility [60]. Nevertheless, HIV-1 superinfections are more frequently detected when two distinct regions of the viral genome rather than one are sequenced, and samples from different time points analyzed [52,54,62]. Finally, a major drawback of population-based sequencing is its lack of sensitivity to detect strains that are underrepresented in the quasi species population, and alternative methods, such as heteroduplex mobility assay and ultra-deep sequencing, might be more appropriate to detect superinfections [63][64][65].…”

Section: What Is the Incidence Of Hiv-1 Superinfection?mentioning

confidence: 99%

“…However, despite the flourishing literature on the subject, there is a current lack of technology and available data to clearly determine the incidence of this phenomenon. Cross-sectional studies [51] or longitudinal follow-ups with limited sampling over time [52] might not represent adequate settings to assess superinfection incidence rates. Combined with a lack of adequately sensitive techniques to reliably identify this event, the true prevalence of superinfection is likely to be underestimated and still subject to intense controversy (reviewed in [53]).…”

Section: What Is the Incidence Of Hiv-1 Superinfection?mentioning

confidence: 99%

Socioeconomic Impact of HIV/AIDS on Households under Free Antiretroviral Therapy in Preah Sihanouk Province, Cambodia

Nomoto¹

2012

J Antivir Antiretrovir

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Multiple-infection and recombination in HIV-1 within a longitudinal cohort of women

Cited by 38 publications

References 35 publications

Impact of Clade, Geography, and Age of the Epidemic on HIV-1 Neutralization by Antibodies

Impact of Clade, Geography, and Age of the Epidemic on HIV-1 Neutralization by Antibodies

Longitudinal Quasispecies Analysis of Viral Variants in HIV Type 1 Dually Infected Individuals Highlights the Importance of Sequence Identity in Viral Recombination

Socioeconomic Impact of HIV/AIDS on Households under Free Antiretroviral Therapy in Preah Sihanouk Province, Cambodia

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