The human immunodeficiency virus (HIV) was first transmitted from chimpanzees to humans around 100 years ago, and in that relatively short time, it has become one of the greatest infectious disease threats facing the world today. Today, HIV is transmitted primarily through sexual contact or mother-to-child transmission. After infection, HIV impairs the immune system leaving the host unable to properly defend itself from pathogens or opportunistic diseases, such as tuberculosis.

Work in the Sodora Lab primarily focuses on two principal areas of HIV research: HIV transmission and HIV-induced disease and immune factors that impact progression to AIDS. Collectively, these research strategies are designed to produce novel vaccine approaches and immune therapies that will decrease the spread of HIV and/or prevent disease progression in HIV-infected people.

Factors Involved With Mother-to-Child Spread of HIV

Understanding how HIV is transmitted from one person to another is a critical step in developing an efficacious vaccine. The transmission project in the Sodora Lab focuses on the oral transmission of HIV from mother to child, as well as the host immune factors that may affect HIV acquisition in infants. The foundation of this project is seminal studies from the Sodora Lab, evaluating the earliest events following oral HIV transmission; the majority of these studies have utilized the simian immunodeficiency virus (SIV) macaque animal model. Our current studies assess factors that activate the immune system and can impact the transmission of HIV from mothers to babies. One type of immune activation with which infants are exposed are the standard vaccine regimens given to protect against a number of infectious diseases. One vaccine of interest is the BCG vaccine, which offers protection against tuberculosis. Our previous work demonstrated that human infants immunized with BCG had increased immune activation of HIV target cells, suggesting that BCG may be resulting in an immune environment that is more permissive to HIV infection. Our ongoing study is to utilize the SIV-macaque model to unravel the immune mechanisms that may impact HIV transmission after BCG vaccination, including an increase in immune activation and an expansion of HIV target cells.

A second ongoing study in the Sodora Lab evaluates how different feeding practices may impact HIV transmission in infants. These studies involve evaluating samples from South African infants that are either exclusively breastfed or mixed-fed (breast milk and cereal or formula); mixed feeding is associated with an 11-fold increased risk of acquiring HIV transmission. The study is designed to provide mechanistic understanding into this observation that is quite perplexing. Presently, we are evaluating how the introduction of non-breast milk foods to infants could potentially alter HIV-target cells in these South African infants.

The long-term goal of this research is to identify the immune changes at the site of transmission that impact the frequency of a successful transmission event, and to utilize the findings to aid in the development of an HIV vaccine designed to prevent transmission of HIV.

Assessing HIV-Induced Disease Progression

HIV entry into the human population began as a zoonotic transmission, from a different species into humans. In the case of HIV, the SIV virus is naturally found in a number of African monkeys and chimpanzees. SIV in its natural monkey hosts is very different compared to when it infects humans. Generally, these monkeys do not develop any clinical signs of disease. This is particularly perplexing as the virus is able to replicate at high levels in monkeys, yet somehow, the monkeys have learned to live with this infection. Studying one of these monkey species, sooty mangabeys, the Sodora Lab was the first to demonstrate that in addition to being OK with high levels of replication, natural hosts are also able to function just fine with low levels of CD4+ T cells. This was a surprising finding, and the lab set out to understand which compensatory mechanisms are in place that allowed mangabeys to immunologically function with very low levels of this key immune cell. What they found was that an understudied immune T cell subset, double-negative T cells have the potential to compensate for CD4 T cell loss and can provide essential immune functions in sooty mangabeys. These cells are called “double negative” because they lack two proteins normally associated with T cell function, CD4 and CD8. What is particularly fascinating with regard to utilizing these cells to compensate for the absence of CD4 cells is that double-negative T cells are resistant to HIV infection (because they lack the CD4 protein). Currently, our lab focuses on characterizing double-negative T cells in humans and determining the potential of these cells to improve immune responses during HIV infection. We believe that harnessing the full potential of double-negative T cells will assist in the restoration of immune competence and decrease the risk of opportunistic pathogens in HIV-infected patients.

About Dr. Don Sodora

Don Sodora, PhD, is a professor at the Center for Global Infectious Disease Research. He joined in 2007 to advance the center’s mission in the field of HIV research. Don received his PhD in microbiology from the University of Pennsylvania. He performed postdoctoral research at Stanford University and the Aaron Diamond AIDS Research Center in New York. Sodora has collaborators in Atlanta, Philadelphia, Oregon, Northern Ireland and Cape Town, South Africa. He is dedicated to the training of undergraduate and graduate students, including serving on the Graduate Student Advisory Committee for the Pathobiology Graduate Program at the University of Washington. Outside of the lab, he enjoys spending time with his friends and family, traveling, hiking, taking photographs and camping.