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Dynamics of HIV type 1 recombination following superinfection.

ABSTRACT: There are currently few detailed studies describing HIV-1 recombination events or the potential impact of recombination on drug resistance. We describe here the viral recombination dynamics in a drug-naive patient initially infected with a circulating recombinant form 19 (CRF19) virus containing transmitted drug resistance mutations followed by superinfection with "wild-type" subtype B virus. Single genome analysis showed replacement of the primary CRF19 virus by recombinants of the CRF19 virus and the superinfecting subtype B virus. The CRF19/B recombinant virus dominating after superinfection had lost drug resistance mutations and at no time was the superinfecting subtype B variant found to be dominant in blood plasma. Furthermore, the detection of recombinant viruses in seminal plasma indicates the potential for onward transmission of these strains.

SUBMITTER: Koning FA

PROVIDER: S-EPMC3653373 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Dynamics of HIV type 1 recombination following superinfection.

Koning Fransje A FA Badhan Anjna A Shaw Simon S Fisher Martin M Mbisa Jean L JL Cane Patricia A PA

AIDS research and human retroviruses 20130418 6

There are currently few detailed studies describing HIV-1 recombination events or the potential impact of recombination on drug resistance. We describe here the viral recombination dynamics in a drug-naive patient initially infected with a circulating recombinant form 19 (CRF19) virus containing transmitted drug resistance mutations followed by superinfection with "wild-type" subtype B virus. Single genome analysis showed replacement of the primary CRF19 virus by recombinants of the CRF19 virus ...[more]

PMID: 23495713

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Project description:A series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a recombination structure analysis of the gag, pol, and nef genes from longitudinal samples of patient LNA819. A total of 9 pol and 5 nef CRF01_AE/CRF07_BC recombinants were detected. The quasispecies makeup and the composition of the pol and nef gene recombinants changed continuously, suggestive of continuous evolution in vivo. T-cell responses targeting peptides of the primary strain and the recombination regions were screened. The results showed that Pol-LY10, Pol-RY9, and Nef-GL9 were the immunodominant epitopes. Pol-LY10 overlapped with the recombination breakpoints in multiple recombinants. For the LY10 epitope, escape from T-cell responses was mediated by both recombination with a CRF07_BC insertion carrying the T467E/T472V variants and T467N/T472V mutations originating in the CRF01_AE strain. In pol recombinants R8 and R9, the recombination breakpoints were located ~23 amino acids upstream of the RY9 epitope. The appearance of new recombination breakpoints harboring a CRF07_BC insertion carrying a R984K variant was associated with escape from RY9-specific T-cell responses. Although the Nef-GL9 epitope was located either within or 10~11 amino acids downstream of the recombination breakpoints, no variant of this epitope was observed in the nef recombinants. Instead, a F85V mutation originating in the CRF01_AE strain was the main immune escape mechanism. Understanding the cellular immune pressure on recombination is critical for monitoring the new circulating recombinant forms of HIV and designing epitope-based vaccines. Vaccines targeting antigens that are less likely to escape immune pressure by recombination and/or mutation are likely to be of benefit to patients with HIV-1.

Dataset Information

Dynamics of HIV type 1 recombination following superinfection.

Publications

Dynamics of HIV type 1 recombination following superinfection.

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