HIV, EBV and KSHV: Viral cooperation in the pathogenesis of human malignancies

Malignancies associated with Epstein-Barr virus (EBV) and/or Kaposi's sarcoma human herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is frequently found in patients infected with HIV. Both these human gammaherpesviruses are known for their oncogenic properties, for the viral products that mimic or interfere with the functions of critical cellular proteins, and the ability to escape the immune responses. The introduction of the highly active anti-retroviral therapy (HAART) has significantly decreased the frequency of Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL), and primary central nervous system lymphoma (PCNSL); conversely, for some lymphomas the incidence diminished only slightly, as in Burkitt's lymphoma (BL), or had no significant variations, as Hodgkin's lymphoma (HL). These observations may indicate that HAART might have a direct impact on KSHV and EBV biology, that there is a reconstitution of the immune system in HIV-infected patients under HAART, or even that HAART perhaps has a detrimental impact in the pathogenic interactions between HIV, EBV and KSHV. The present review aim to evaluate and to discuss the data available for these hypotheses, in order to shed more light on the mechanisms for the cooperation among HIV-1, EBV and KSHV that may culminate in cell transformation and cancer development in humans.