Abstract
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.
Highlights
Epstein-Barr Virus (EBV) is a ubiquitous virus infecting over 90% of adults in developed and developing countries [1]
Using a humanized mouse model of EBV infection [14– 17], we directly demonstrated that HIV co-infection enhances systemic EBV replication, immune activation, and EBV-induced tumorigenesis in vivo
These data are consistent with studies reporting increased detection of EBV-DNA in the peripheral blood and saliva and the increased incidence of certain types of EBV-associated cancers in people living with HIV (PLWH) without any interventions [6– 8, 18–21]
Summary
Epstein-Barr Virus (EBV) is a ubiquitous virus infecting over 90% of adults in developed and developing countries [1]. EBV is an oncogenic herpesvirus that primarily infects B cells [2– 4]. Primary infection is characterized by the rapid proliferation of infected B cells until an effective immune response is elicited and/or EBV-infected B cells differentiate into latently-infected memory-like cells establishing a life-long infection of the B cell compartment [2–4]. EBV maintains a latent infection with intermittent periods of subclinical virus reactivation and shedding [5]. EBV can induce the formation of B cell lymphomas in immune suppressed individuals including people living with HIV (PLWH) [4, 6, 7]. EBV positive PLWH have over a 60-fold higher risk of developing lymphomas compared to the general population
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call