Short Communication: A Recombinant Variant with Increased Envelope Entry Efficiency Emerged During Early Infection of an HIV-1 Subtype C Dual Infected Rapid Progressor.
AIDS Res Hum Retroviruses
; 32(3): 303-10, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-25905681
ABSTRACT
Mutations in functionally constrained sites of the HIV envelope (Env) can affect entry efficiency and are potential targets for vaccine and drug design. We investigated Du151, a dual-infected individual with rapid disease progression. At her death 19 months postinfection (mpi), she was infected with a recombinant variant, which outgrew both parental viruses. We aimed to determine whether the recombinant virus had enhanced Env entry efficiency compared to the parental viruses and to identify the functional determinant. We generated 15 env clones at 1, 2, 8, and 19 mpi. Pseudovirus carrying a recombinant Env clone (PSV clone), C18 (19 mpi), had significantly higher entry efficiency compared to the parents, suggesting that the recombinant virus had enhanced fitness. To identify the functional determinant, we compared two recombinant PSV clones (C18 and C63)-differing in entry efficiency (2-fold) and by four and three amino acids in gp120 and gp41, respectively. The increased entry efficiency of a C18-gp41 PSV chimera indicated that the three amino acids in the C18 gp41 region were involved (K658, G671, and F717). Site-directed mutagenesis of the three amino acids of C63 showed that a single amino acid mutation, R658K, increased pseudovirion entry efficiency. The introduction of R658 into two PSV clones (C1 and C18) decreased their entry efficiency, suggesting that R658 carries a fitness cost. Thus, our data suggest that a recombinant virus emerged at 19 mpi with enhanced Env entry efficiency. Therefore, K658 in gp41 could in part be a contributing factor to the increased viral load and rapid disease progression of Du151.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Recombinação Genética
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Infecções por HIV
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HIV-1
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Internalização do Vírus
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Produtos do Gene env do Vírus da Imunodeficiência Humana
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article