Recombination-mediated escape from primary CD8+ T cells in acute HIV-1 infection

Ritchie, Adam; Cai, Fangping; Smith, N.; Chen, Sheri; Song, Hongshuo; Brackenridge, Simon; Karim, Salim S. Abdool; Korber, Bette; McMichael, Andrew J.; Feng, Gao; Goonetilleke, Nilu

doi:10.1186/preaccept-1035836021115701

Cited by 9 publications

(11 citation statements)

References 37 publications

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“…populations, with only a few single base selection sites, which is typically observed as in our previous analysis of acute/early infection during the first 2 months of infection in adults (Gao et al, 2014;Liu et al, 2013;Ritchie et al, 2014). Thus, our results demonstrate that diversity in these long-term in utero infections was driven by recombination and new mutations mainly accumulated during pregnancy, not after birth.…”

Section: Discussionsupporting

confidence: 81%

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Marichannegowda

Mengual

Kumar

et al. 2020

Preprint

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SummaryStudy of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 env gene from 12 in utero transmission pairs show that most infections (67%) occur within two months from childbirth. In addition, env sequences from long-term infected fetuses were highly divergent and formed separate phylogenetic lineages from their cognate maternal viruses. Host selection sites unique to infant viruses were identified in regions frequently targeted by broadly neutralizing antibodies and T cell immune responses. The identification of unique selection sites in the env gene of fetal viruses indicates that the immune system in fetuses is capable of exerting selection pressure on viral evolution. Studying selection and evolution of HIV-1 or other viruses in fetuses can be an alternative approach to investigate adaptive immunity in fetuses.

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Section: Discussionsupporting

confidence: 81%

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Marichannegowda

Mengual

Kumar

et al. 2020

Preprint

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“…This rate is within range of that of reported HIV mutation rates (Abram et al, 2010; Ji and Loeb, 1992; Roberts et al, 1988). Recombination has been found to mediate escape from ART (Kellam and Larder, 1995; Moutouh et al, 1996), CD8 + T cells (Ritchie et al, 2014; Streeck et al, 2008), and autologous neutralizing antibodies (Chaillon et al, 2013; Moore et al, 2013; Song et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

Cohen

Lorenzi

Krassnig

et al. 2018

Preprint

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SummaryIn the setting of a clinical trial evaluating the anti-HIV-1 antibody 3BNC117, Cohen et al. demonstrate that rebound viruses that emerge following interruption of antiretroviral therapy are distinct from circulating latent viruses. However, rebound viruses often appear to be recombinants between isolated latent viruses. By incorporating the possibility of recombination, 63% of the rebound viruses could have derived from the observed latent reservoir. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating reservoir, but instead appear to represent recombinants. AbstractAll rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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“…RNA recombination is thought to benefit viruses by accelerating combination of beneficial mutations from different lineages (9,10) and/or by purging of deleterious mutations (11,12). Studies in HIV-1 have shown that recombination contributes to the acquisition of multidrug resistance (13,14) and immune escape (15,16), demonstrating the potential advantage of recombination in speeding up production of adaptive genotypes. However, because RNA viruses exhibit high mutation rates and thus may readily generate advantageous combinations by mutation alone, the relative contribution of recombination is unclear.…”

Section: Introductionmentioning

confidence: 99%

Genetic recombination of poliovirus facilitates subversion of host barriers to infection

Acevedo

Woodman

et al. 2018

Preprint

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The contribution of RNA recombination to viral fitness and pathogenesis is poorly defined. Here, we isolate a recombination-deficient, poliovirus variant and find that, while recombination is detrimental to virus replication in tissue culture, recombination is important for pathogenesis in infected animals. Notably, recombination-defective virus exhibits severe attenuation following intravenous inoculation that is associated with a significant reduction in population size during intra-host spread. Because the impact of high mutational loads manifests most strongly at small population sizes, our data suggest that the repair of mutagenized genomes is an essential function of recombination and that this function may drive the long-term maintenance of recombination in viral species despite its associated fitness costs. Significance StatementRNA recombination is a widespread but poorly understood feature of RNA virus replication. For poliovirus, recombination is involved in the emergence of neurovirulent circulating vaccinederived poliovirus, which has hampered global poliovirus eradication efforts. This emergence illustrates the power of recombination to drive major adaptive change; however, it remains unclear if these adaptive events represent the primary role of recombination in virus survival. Here, we identify a viral mutant with a reduced rate of recombination and find that recombination also plays a central role in the spread of virus within animal hosts. These results highlight a novel approach for improving the safety of live attenuated vaccines and further our understanding of the role of recombination in virus pathogenesis and evolution.

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Recombination-mediated escape from primary CD8+ T cells in acute HIV-1 infection

Abstract: Background: A major immune evasion mechanism of HIV-1 is the accumulation of non-synonymous mutations in and around T cell epitopes, resulting in loss of T cell recognition and virus escape.

Cited by 9 publications

References 37 publications

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

Genetic recombination of poliovirus facilitates subversion of host barriers to infection

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