Biological characterization of natural and artificial HIV-1 recombinants between subtypes B and F

Abstract

Despite efforts to control the epidemic spread of HIV, the high diversity of recombinant forms may have been associated to the increase of infected people around the globe. In Brazil, many recombinant viruses have been described, and up to this moment, 5 circulant recombinant forms (CRF) have already been described (CRF28_BF, CRF29_BF, CRF39_BF, CRF40_BF, CRF46_BF). This fact indicates the relevance of recombinant forms in the Brazilian epidemic. In spite of their increasing epidemiological importance, little is known about cell tropism, drug resistance, replicative and transmission capacity of the recombinant viruses in our epidemics. This project aims to study some relevant aspects of the biology of recombinant forms of HIV-1 circulating in São Paulo State that were sampled during Viral Genetic Diversity Network program (funded by FAPESP). Initially, we will aim to isolate through co-cultivation exemplars of CRF28_BF and CRF29_BF and some additional unique recombinant forms. In order to confirm the recombination profile and particular genetic signatures, the genome of each isolate will be throroughly sequenced. After that, co-receptor usage of each isolate will be determined using both genotyping and phenotyping methods. Likewise, the resistance profile of viral reverse transcriptases and proteases will be determined by genotyping and phenotyping methods. Moreover, resistant proteases will be reconstructed in silico for inhibitor interaction simulations during molecular dynamics. In addition, some selected proteases will be phenotyped by means of their insertion and expression in recombinant HIV during cell infection experiments. (AU)