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 aggressive metastatic ARL, and 3) HIV gene flow among lymph nodes, normal and metastatic tissues was non-random. The different population dynamics between the viruses found in tumors versus the non-tumor associated viruses suggest that there is a significant relationship between HIV evolution and lymphoma pathogenesis. Moreover, the study indicates that HIV could be used as an effective marker to study the origin and dissemination of lymphomas in vivo.
Highlights
AIDS related lymphoma (ARL) is a disease that occurs in 3–4% of patients infected with the human immunodeficiency virus (HIV) despite the initiation of highly active antiretroviral therapy (HAART) [1]
Our results show that a subset of the tumor-associated macrophages (TAM) identified with CD68 staining was positive for HIV p24 (Figure 1)
The present study is the first to investigate HIV-1 evolutionary patterns among tissues from lymphoma patients and to demonstrate the existence of a distinct viral sub-population at least in part associated with TAMs
Summary
AIDS related lymphoma (ARL) is a disease that occurs in 3–4% of patients infected with the human immunodeficiency virus (HIV) despite the initiation of highly active antiretroviral therapy (HAART) [1]. Since the introduction of HAART, the overall incidence of ARL has been reduced approximately 50%; it still occurs at a rate much higher than in non-HIV infected individuals, suggesting a viral component is involved in the development of ARL [1]. The primary difference between lymphoma in non-HIV infected individuals and ARL is that ARLs are uniformly high grade and widely metastatic, with death occurring in as little as two weeks after diagnosis [2]. In non-AIDS settings, patients with follicular lymphoma containing high levels of tumor-associated macrophages (TAM) progress more rapidly than patients with fewer TAM [7,8,9,10]
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