In most individuals, EBV maintains a life-long asymptomatic
latent infection. However, EBV can induce the formation of
B cell lymphomas in immune suppressed individuals including people living with HIV (PLWH). Most individuals who acquire HIV are already infected with EBV as
EBV infection is primarily acquired during childhood and adolescence. Although antiretroviral
therapy (ART) has substantially reduced the incidence of
AIDS-associated
malignancies, EBV positive PLWH are at an increased risk of developing
lymphomas compared to the general population. The direct effect of HIV
co-infection on EBV replication and EBV-induced
tumorigenesis has not been experimentally examined. Using a humanized mouse model of
EBV infection, we demonstrate that HIV
co-infection enhances systemic EBV replication and immune activation. Importantly, EBV-induced
tumorigenesis was augmented in EBV/HIV co-infected mice. Collectively, these results demonstrate a direct effect of HIV
co-infection on EBV pathogenesis and
disease progression and will facilitate future studies to address why the incidence of certain types of EBV-associated
malignancies are stable or increasing in ART treated PLWH.