Understanding HIV Transmission and Progression to AIDS

Studying mucosal immunology for novel approaches to vaccines and immunotherapies

Technical overview

Dr. Donald Sodora

Current evidence on how HIV infection progresses to AIDS suggests that the viral infection results in chronic immune activation and inflammation that plays a major role in the development of AIDS. This model provides insights as to why the HIV disease course differs among people with the same virus: Each person’s immune system reacts differently to the disease agent. An ongoing area of research in the Sodora laboratory is studying how immune activation and inflammation affect HIV disease outcomes.

Dr. Sodora is interested in how multiple factors affect HIV transmission, infection, and the development of AIDS. For example, a leading contributor to morbidity and mortality in people infected with HIV is co-infection with mycobacteria, including Mycobacterium tuberculosis, the cause of tuberculosis. A particular focus of the Sodora group is studying how mycobacterial infections influence the HIV disease course.

Dr. Sodora is also interested in HIV vaccine development, including an assessment of how mucosal immunology, especially inflammation, influences the chance that an exposure to HIV will result in a successful HIV infection . As part of this work, his group is studying mucosal sites as a novel approach to delivering HIV vaccines.

Dr. Sodora’s group has experience working with model organisms including a simian immunodeficiency virus-infected Rhesus macaque model. The researchers have used the model for HIV vaccine development to study the effects of antiretroviral therapy, and to determine how HIV infection and the presence of mycobacteria affect the immune system. Their expertise includes analyzing immune cell gene expression and blood biomarkers. This work has identified transcriptomic and cytokine signatures associated with HIV infection and mycobacterial co-infection.

Stage of Development

• Preclinical in vitro
• Preclinical in vivo
• Preclinical ex vivo

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Consultation agreement

Publications

Fisher BS, Green RR, Brown RR, Wood MP, Hensley-McBain T, Fisher C, Chang J, Miller AD, Bosche WJ, Lifson JD, Mavigner M, Miller CJ, Gale M Jr, Silvestri G, Chahroudi A, Klatt NR, Sodora DL. Liver macrophage-associated inflammation correlates with SIV burden and is substantially reduced following cART. PLoS Pathog. 2018;14:e1006871

Gasper MA, Biswas SP, Fisher BS, Ehnert SC, Sherman DR, Sodora DL. Nonpathogenic SIV and Pathogenic HIV Infections Associate with Disparate Innate Cytokine Signatures in Response to Mycobacterium bovis BCG. PLoS One. 2016;11: e0158149.

Sundaravaradan V, Saleem R, Micci L, Gasper MA, Ortiz AM, Else J, Silvestri G, Paiardini M, Aitchison JD, Sodora DL. Multifunctional double-negative T cells in sooty mangabeys mediate T-helper functions irrespective of SIV infection. PLoS Pathog. 2013; 9: e1003441.

Milush JM, Mir KD, Sundaravaradan V, Gordon SN, Engram J, Cano CA, Reeves JD, Anton E, O'Neill E, Butler E, Hancock K, Cole KS, Brenchley JM, Else JG, Silvestri G, Sodora DL. Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells. J Clin Invest. 2011 Mar;121(3):1102-10

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