HIV's Disease-producing Potential is Influenced by Two Factors

HIV/AIDS researchers at the Emory University School of Medicine have conducted a new study that reflects the balance between the ability of the virus to remain invisible to the immune system, when newly infecting the host with HIV, and its ability to replicate; the balance between these two factors influence the speed of disease progression, according to the press release.

HIV remains a worldwide public health concern, especially in underdeveloped countries that do not have effective prevention and treatment efforts readily available. The study, published in Journal of Experimental Medicine, was made possible due to the Zamia-Emory HIV Research Project, a project that aims to provide education and prevention to couples in sub-Saharan Africa, where the majority of new HIV infections are acquired by spouses or long term partners. According to their website, 70% of new HIV infections are estimated to occur in Zambia in couples who are unaware that their partner is HIV-positive. Through their Couples Voluntary Counseling and Testing program, researchers aim to advance HIV education and reduce transmission by proving prevention and treatment options.

In this study, the researchers analyzed HIV transmission in 169 heterosexual couples in Zambia. They found that around a third of possible target sites linked to HLA proteins, proteins that are responsible for immune system regulation, were “pre-adapted” to the immune response of the partner who was newly infected with the HIV virus; this pre-adaption means that the HIV virus has already mutated or evolved to avoid immune system detection. Keeping these findings in mind, researchers feel that the focus when it comes to HIV vaccination development should be on “regions of conserved viral proteins that do not become adapted in the same way,” according to the press release.

This analysis follows up on previous research on the transmission event, conducted by Eric Hunter, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine, Emory Vaccine Center and Yerkes National Primate Research Center, who also led this study. According to Dr. Hunter, when it comes to HIV, the virus is constantly mutating and there is a “tug of war” between the avoiding immune system detection and experiencing changes that impair the virus’s ability to reproduce. According to the press release, “Both of these factors influence the level of virus found in blood and how quickly it can induce CD4 T cell loss and progression to AIDS in the newly-infected person.”

HLA proteins contain pieces of viral proteins that cytotoxic cells, CD8+ T cells, can target and eliminated infected cells. These proteins are different in every person but their purpose is the same in everyone; human genes encode HLA proteins in order to direct immune system response to HIV. In response to this target and elimination process, the virus mutates the pieces of viral proteins in the HLA proteins so that they will avoid immune system detection.

Daniela C. Mónaco, PhD, first author of the study and postdoctoral fellow at Emory University School of Medicine, said, “There’s a critical balance between viral polymorphisms that reduce immune recognition and others that negatively influence replicative fitness. By taking both into account, we could better estimate the overall impact on viral load and disease progression.”