Pathogenesis of HIV-associated non-Hodgkin lymphoma.
In the current era of highly active antiretroviral therapy (HAART), the prevalence of HIV-associated non-Hodgkin lymphoma (H-NHL) is not as high as in the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, but still remains above that of non-HIV-infected individuals. Therefore, the epidemiology suggests that the pathogenesis of H-NHL may be multifactoral, involving the interaction of the immune system with HIV or other pathogens. Although HIV is a retrovirus, it is not characterized with the typical oncogenic potential associated with insertional mutagenesis. HIV integration occurs as a necessary step in the life cycle allowing for replication and transcription of the viral genome to take place. While HIV is thought to integrate randomly, more recent studies have suggested that integration occasionally occurs in a less random fashion. While the majority of H-NHL may be secondary to immune dysfunction, this non-random integration may be a factor leading to pathogenesis of a small subset of H-NHL since the pathways involved in malignancies usually require an accumulation of abnormalities leading to proliferation and transformation. A common element among lymphomas in this setting of immune dysfunction is the inability to control a pathogen that acts as an ongoing immune activator. Thus, an increased risk of H-NHL emerges from the combination of immunodeficiency, increased immune activation and possible HIV insertional mutagenesis. The focus of this review will be on the role viral pathogenesis plays in oncogenic transformation.
Killebrew
Deirdre
D
Retrovirology Research Laboratory, Leahi Hospital, Young Bldg., 5th Fl., 3675 Kilauea Ave., Honolulu, HI 96816, USA. dak@hawaii.edu
Shiramizu
Bruce
B
D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D015415:Biomarkers; D002472:Cell Transformation, Viral; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D019288:Herpesvirus 8, Human / Q000302:isolation & purification; D006801:Humans; D007121:Immunocompetence; D016483:Lymphoma, AIDS-Related / Q000209:etiology / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000208:ethnology / Q000209:etiology* / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D012307:Risk Factors; D016662:Virus Integration
D015415:Biomarkers