M. tuberculosis co-infection and immunity affects SIV diversity in LN and granulomas

Approximately 38 million people worldwide are infected with HIV and they are 20 times more likely to become ill with tuberculosis (TB) than uninfected individuals. HIV co-infection with Mycobacterium tuberculosis (Mtb), the etiologic bacterium that causes TB, is the leading cause of death among people living with HIV.

In collaboration with the laboratories of Ling Lin and Pleuni Pennings, Chris performed next generation sequencing of SIV RNA in the blood and different tissues from macaques with latent Mtb and co-infected with SIV, a model of HIV/Mtb co-infection (previously published in Diedrich et al.), and reported our findings in the journal Viruses. Early after nonpathogenic SIV infection, some animals continued to have latent Mtb infection but some animals had reactivation of Mtb infection. Our goal was to investigate changes in the virus population in the blood and several different tissue compartments in animals infected with SIV only or with Mtb co-infection with or without evidence of TB reactivation.

SIV diversity was higher in co-infected macaques that did not develop Mtb reactivation and was highest in thoracic lymph nodes that drain the lungs, suggesting that SIV replication can be higher and compartmentalized in these sites of TB disease. Thoracic lymph nodes may be important for dissemination of Mtb during co-infection, contributing to the greater incidence of extrapulmonary disease in co-infected individuals.

In lung granulomas, viral diversity was positively correlated with the frequency of CD4+ T cells but negatively correlated with the frequency of granzyme B expressing CD8+ T cells. CD8+ T cells reduce virus replication. Because SIV replication is required for increased genetic diversity, we hypothesize that higher CD8+ T cell responses and lower viral replication during acute SIV infection is associated with lower viral diversity.