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Research Article: Differential Distribution and Evolution of HIV-1 RNA Variants in the Gastrointestinal Tract of Antiretroviral Naive African AIDS Patients with Diarrhea and (or) Weight Loss

Phetole Mahasha*, Edana Cassol,, Siva Danaviah, Robert Bond, Christopher Seebregts, Schalk W. van der Merwe, Theresa Rossouw and Tulio de Oliveira*

Background: Obtaining samples of the gastrointestinal tract (GIT) is difficult. As a result, little is known about the diversification and genetic evolution of Human Immunodeficiency Virus-1 (HIV-1) in the GIT. Here, we evaluated the diversity and phylogenetic relationships among HIV-1 RNA quasispecies derived from the duodenum, jejunum, ileum, right colon, left colon and plasma of antiretroviral therapy (ART)-naive South African AIDS patients infected with HIV-1 subtype C. A total of 45 pol and 350 cloned gag and env Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) fragments were sequenced and subjected to phylogenetic analysis.

Results: Significant differences were observed in the diversity, evolution and trafficking of HIV-1 RNA quasispecies in the small vs. large intestine. Env Ribonucleic acid (RNA) variants were the most diverse with the small intestine exhibiting the highest level of diversity. Gag RNA variants exhibited low levels of diversity in all tissues. Migration and exchange of HIV-1 RNA variants between plasma and different regions of the GIT was more evident in gag than in env trees. Some env variants formed tight monophyletic clusters of closely related viral quasispecies suggesting there was localized replication and adaptive evolution of the env gene, primarily in the colon, but also in the small intestine of some patients. Analysis of inferred amino acid sequences indicated that some pol sequences contained substitutions in protein domains associated with altered susceptibility to ART. A small number of differentially distributed env variants had substitutions that are known to alter the neutralization and co-receptor binding properties of the V3 loop.

Conclusions: Diversification of HIV-1 in the GIT of ART-naive AIDS patients is a highly dynamic process involving localized, tissue-specific evolution in addition to extensive exchange of HIV-1 RNA variants between plasma and different gut compartments.

Cite this Article: Mahasha P, Cassol E, Danaviah S, Bond R, Seebregts C, et al. Laboratory diagnosis reliability and quality assurance system. SRL Virol Infect Dis. 2015;1(1): 004-016.

Published: 31 December 2015

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