distinct patterns of hiv-1 evolution within metastatic tissues in patients with non-hodgkins lymphoma不同模式的hiv - 1在转移性非霍奇金淋巴瘤患者的组织演变.pdfVIP

Distinct Patterns of HIV-1 Evolution within Metastatic Tissues in Patients with Non-Hodgkins Lymphoma 1 2 3 3 1 Marco Salemi *, Susanna L. Lamers , Leanne C. Huysentruyt , Derek Galligan , Rebecca R. Gray , Alanna 3 3 Morris , Michael S. McGrath * 1 Department of Pathology Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America, 2 BioInfoExperts, Thibodaux, Louisiana, United States of America, 3 Department of Medicine, Hematology and Oncology, University of California San Francisco, San Francisco, California, United States of America Abstract Despite highly active antiretroviral therapy (HAART), AIDS related lymphoma (ARL) occurs at a significantly higher rate in patients infected with the Human Immunodeficiency Virus (HIV) than in the general population. HIV-infected macrophages are a known viral reservoir and have been shown to have lymphomagenic potential in SCID mice; therefore, there is an interest in determining if a viral component to lymphomagenesis also exists. We sequenced HIV-1 envelope gp120 clones obtained post mortem from several tumor and non-tumor tissues of two patients who died with AIDS-related Non- Hodgkin’s lymphoma (ARL-NH). Similar results were found in both patients: 1) high-resolution phylogenetic analysis showed a significant degree of compartmentalization between lymphoma and non-lymphoma viral sub-populations while viral sub- populations from lymph nodes appeared to be intermixed within sequences from tumor and non-tumor tissues, 2) a 100- fold increase in the effective HIV population size in tumor versus non-tumor tissues was associated with the emergence of lymphadenopathy and aggr