Sujan Shresta

Associate professor

Sujan Shresta, Ph.D., and her team study the immunology and virology of dengue virus (DENV) and Zika virus (ZIKV), both globally important mosquito-borne human pathogens. DENV causes a spectrum of clinical disease ranging from Dengue Fever (DF), a self-limited febrile illness, to a life-threatening syndrome called Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS). ZIKV has been proven to cause serious birth defects, and is also being investigated for associations with other neurological conditions including Guillain-Barré Syndrome (GBS) and meningoencephalitis.

Studies suggest that the host’s immune system plays plays a dual role in protection and pathogenesis; however, how the immune response to DENV and ZIKV protects against or contributes to severe disease remains unclear and controversial. Using mouse models and human cell culture models, Dr. Shresta and her team dissect the protective versus pathogenic mechanisms of the immune system in response to these viral infections. Using gene-targeted mice and human cells that lack specific components of the immune system, a better understanding of the immune response to DENV and ZIKV is critical for developing much-needed vaccines and antivirals.

A second line of research involves the identification of viral components that modulate the severity of DENV and ZIKV infection in infants. Dr. Shresta and her team have isolated new DENV and ZIKV strains in mice by adapting viral isolates from humans and mosquitoes into peripheral tissues of mice. Using a reverse-genetics system, in which specific viral sequences are manipulated within the context of a full-length infectious clone of the virus, they have been defining the roles of particular viral components in influencing DENV and ZIKV infection in mice and human cells. As both DENV and ZIKV are increasingly spreading from tropical to temperate zones worldwide, the team has also begun to investigate DENV evolution in Nepal and ZIKV sexual transmission. Knowledge of the viral determinants of severe dengue and Zika disease, climatic zone shifts, and viral genetic variation may provide novel avenues for developing DENV- and ZIKV-specific therapeutics.