EVOLUTION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 CLADE C ENVELOPE V1-V5 REGION DURING DISEASE PROGRESSION IN NON-HUMAN PRIMATE MODEL

Human immunodeficiency virus type 1 (HIV-1) clade C strain is the fastest spreading HIV-1 strain globally, especially in Africa. It has been decades since the acquired immune deficiency syndrome (AIDS) pandemic first started. However, an effective anti-HIV-1 vaccine is not yet available, which is partly due to the highly variable nature of HIV-1 envelope gene and the absence of a suitable animal model. Strengthening of the understanding of envelope evolution during disease progression will contribute significantly towards future anti-HIV-1 treatment and preventions. Non-human primates have been an essential animal model for many biomedical research areas. Using simian-human immunodeficiency virus (SHIV) expressing the HIV-1 clade C V1-V5 envelope regions from Zambia and infecting rhesus macaque, we demonstrated close genetic evolution of the HIV-1 envelope in both non-human primates and patient during disease progression. Utilizing this animal system, we further examined the evolution of the biological properties of HIV-1 envelope and its association with disease progression. In addition, we applied next generation sequencing technology to analyze the genetic evolution of HIV-1 envelope in a different non-human primate, pigtailed macaque, which was infected with a closely related SHIV strain. Our analysis showed that HIV-1 envelope underwent similar genetic evolution through the disease course in three different primate species; the human host and two non-human primate species. In summary, our studies have validated the relevance of SHIV infected non-human primates as the ideal animal model for HIV-1 research. In addition, we have also chronicled the changes in biological characteristics of the HIV-1 envelope through disease progression. Thus, our results underscore the dynamic evolutionary relationships between the intrinsic properties of the HIV-1 envelopes, their evolution and host immune response. Findings from this study may contribute to the eventual resolution of the AIDS pandemic and our knowledge of the roles that HIV-1 envelope plays during disease progression. Advisor: Charles Woo