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Donald Sodora, Ph.D.

		Associate Member Seattle Biomedical Research Institute Email: don.sodora@sbri.org Disease under study: AIDS/HIV

Mission
Dr. Sodora and his colleagues are working to understand how HIV enters body and eventually causes AIDS. His long-term goal is to apply the knowledge gained from his studies to the development of new therapies and vaccines for HIV-infected patients.

Research
Dr. Sodora’s research is focused on correlates of protection against HIV and HIV induced disease, for which he utilizes the SIV monkey model systems. His three areas of research include assessing monkey species, called sooty mangabeys, which do not become clinically ill when infected with SIV; determining immunologic factors that influence oral transmission of HIV/SIV; and developing therapeutics to assist in the recovery of the immune system in SIV infected monkeys treated with antiretroviral therapy (ART).

The first area of research focuses on utilizing the SIV/monkey model to enable an assessment of progression to simian AIDS, which occurs at different rates in different monkey species. For example, sooty mangabeys, a monkey species endemic to West Africa, are SIV infected in the wild and are therefore a natural host. There is evidence that HIV in humans began as a cross-species transmission event when SIV in naturally infected monkeys or chimpanzees passed to humans. The SIV infection of mangabeys represents a riddle in HIV/SIV pathogenesis as the virus replicates to high levels; however, mangabeys generally do not show clinical signs of simian AIDS and have relatively stable CD4 T-cell numbers. The Sodora lab has uncovered important insights into the means by which mangabeys remain free of simian AIDS. The long-term goal is to utilize these findings to identify new therapeutic approaches to assist in immune defense of HIV in humans.

Sodora’s research also focuses on the oral transmission of HIV/SIV, during mother-to-child transmission (via breast milk), as well as oral-genital transmission (via semen). His research focuses on the viral events that occur during the first few days post-infection, specifically viral entry and spread. His lab is also focusing on assessing the innate and adapt immune responses that are triggered through the oral application and subsequent infection of SIV. The longterm goal of this research is to identify the immune changes at the site of transmission that impact the frequency of a successful transmission and to utilize the findings to aid in the development of an HIV vaccine designed to prevent mucosal transmission of HIV.

Sodora’s third project addresses the ability of highly active anti-retroviral therapy (HAART) to function in only a limited manner with regard to immune system recovery in many patients due to the immune degradation imparted from the direct and indirect effects of the previously untreated chronic viral infection. We hypothesize that an effective immune therapy provided concurrently with HAART will result in a more functionally complete immune recovery and a better prognosis for HIV+ patients. Here we test the potential for the cytokine interleukin (IL)-7, which normally functions as a homeostatic regulator to maintain steady T-cell levels, to function as an immune therapeutic. As a cytokine IL-7 is unique in that it has the ability to impact multiple levels of T-cell renewal including in the peripheral circulation as well as thymocyte maturation in the thymus. The approach is to treat SIV+ macaques with HAART alone or HAART with IL-7, to evaluate the ability of IL-7 to influence immune reconstitution. We anticipate that use of the SIV/macaque model will play a key role in the eventual approval of IL-7 as an immune therapeutic for HIV infected patients as well as identify the patient populations most likely to benefit from this therapy.

Themes
     *  HIV events during early infection
     *  HIV animal models
     *  HIV induced immune dysfunction
     *  HIV immune therapy

Dr. Sodora’s research is currently supported by the National Institutes of Health (NIH).

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