HIV-1 Tropism Determines Different Mutation Profiles in Proviral DNA

Autor(es)

Nascimento-Brito, Sieberth ^{[1, 2]} ; Zukurov, Jean Paulo ^[3] ; Maricato, Juliana T. ^[1] ; Volpini, Angela C. ^[4] ; Salim, Anna Christina M. ^[4] ; Araujo, Flavio M. G. ^[4] ; Coimbra, Roney S. ^[5] ; Oliveira, Guilherme C. ^[4] ; Antoneli, Fernando ^{[6, 7]} ; Janini, Luiz Mario R. ^{[3, 1]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, EPM, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

^[2] Univ Fed Rural Rio de Janeiro UFRRJ, Dept Microbiol & Imunol Vet, Rio De Janeiro - Brazil

^[3] Univ Fed Sao Paulo, EPM, Dept Med, Sao Paulo - Brazil

^[4] Fundacao Oswaldo Cruz FIOCRUZ, Res Ctr Rene Rachou CPqRR, Genom & Computat Biol Grp, Belo Horizonte, MG - Brazil

^[5] Fiocruz MS, CPqRR, Biosyst Informat Grp, Belo Horizonte, MG - Brazil

^[6] Univ Fed Sao Paulo, EPM, Dept Informat Saude, Sao Paulo - Brazil

^[7] Univ Fed Sao Paulo, EPM, Lab Biocomplexidade & Genom Evolut, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 9 SEP 28 2015.
• Citações Web of Science: 2

Resumo

In order to establish new infections HIV-1 particles need to attach to receptors expressed on the cellular surface. HIV-1 particles interact with a cell membrane receptor known as CD4 and subsequently with another cell membrane molecule known as a co-receptor. Two major different co-receptors have been identified: C-C chemokine Receptor type 5 (CCR5) and C-X-C chemokine Receptor type 4 (CXCR4) Previous reports have demonstrated cellular modifications upon HIV-1 binding to its co-receptors including gene expression modulations. Here we investigated the effect of viral binding to either CCR5 or CXCR4 co-receptors on viral diversity after a single round of reverse transcription. CCR5 and CXCR4 pseudotyped viruses were used to infect non-stimulated and stimulated PBMCs and purified CD4 positive cells. We adopted the SOLiD methodology to sequence virtually the entire proviral DNA from all experimental infections. Infections with CCR5 and CXCR4 pseudotyped virus resulted in different patterns of genetic diversification. CCR5 virus infections produced extensive proviral diversity while in CXCR4 infections a more localized substitution process was observed. In addition, we present pioneering results of a recently developed method for the analysis of SOLiD generated sequencing data applicable to the study of viral quasi-species. Our findings demonstrate the feasibility of viral quasi-species evaluation by NGS methodologies. We presented for the first time strong evidence for a host cell driving mechanism acting on the HIV-1 genetic variability under the control of co-receptor stimulation. Additional investigations are needed to further clarify this question, which is relevant to viral diversification process and consequent disease progression. (AU)

• Processo FAPESP: 09/14543-0 - Análise da taxa de mutação do vírus da imunodeficiência humana tipo 1 (HIV-1) em ciclo único de infecção in vitro
• Beneficiário: Luiz Mário Ramos Janini
• Modalidade de apoio: Auxílio à Pesquisa - Regular