Research Article: The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi’s Sarcoma, and Non-Hodgkin Lymphoma

Date Published: August 8, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Peter D. Burbelo, Joseph A. Kovacs, Jason Wagner, Ahmad Bayat, Craig S. Rhodes, Yvonne De Souza, John S. Greenspan, Michael J. Iadarola.


Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP), Kaposi’s sarcoma (KS), or non-Hodgkin lymphoma (NHL). Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84%) showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94%) in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.

Partial Text

It is estimated that approximately 18% of all human cancers are caused by infectious agents [1]. A bulk of these cancers are caused by the seven known cancer-associated viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), human T-lymphotropic virus-I (HTLV-I), human papilloma virus (HPV), hepatitis C virus (HCV), Kaposi’s sarcoma herpesvirus (KSHV; also known as HHV-8), and Merkel cell polyomavirus (MCV) [2]. Although HIV is not a cancer-causing virus, HIV-infected individuals are particularly vulnerable for developing several infection-related malignancies compared to the general population [3–6]. Mechanistically, the increase in malignancy seen in AIDS patients is due to HIV-associated immune suppression and the higher rates of infection by several cancer-associated viruses. In particular, HIV-infected individuals show a high incidence of three AIDS-defining malignancies including KSHV-associated Kaposi sarcoma (KS), HPV-driven invasive cervical cancer, and EBV-associated and nonassociated non-Hodgkin lymphoma (NHL). For KS and NHL, there is a 310-fold and 113-fold higher likelihood, respectively, of developing these malignancies in HIV-infected individuals compared to the general population [4]. There are also other malignancies that are considered AIDS associated including anal cancer, lung cancer, testicular germ cell tumors, and Hodgkin disease, which are more common in HIV than in the general population, but the causative agents are less well defined [6, 7].

In this study, the LIPS technology based on luciferase-tagged antigens was employed to generate quantitative antibody profiles against selected antigens from HIV, influenza, and the seven known cancer-associated viruses. To our knowledge, this is the first study to examine infection status and antibody profiles in parallel against these nine different viruses. HIV-infected individuals were the focus of this study since HIV-positive patients are at higher risk for developing a variety of infection-related cancers. Our results with the three groups of HIV patients revealed that 68% of the HIV samples were also coinfected with at least four of the seven cancer-associated viruses (HBV, KSHV, EBV, and MCV). In the case of HBV, the detected antibodies could also reflect patients who have cleared infection. Nevertheless, the high rate of cancer-associated virus exposure was in sharp contrast to the control blood donors who were only infected with the two, EBV and MCV, ubiquitous cancer-associated viruses. Mechanistically the higher antibody levels against EBV and MCV in the HIV-infected patients compared to the healthy controls likely reflects the loss of immune control over these agents resulting in increased viremia and antibody production. On the other hand, these finding for EBV and MCV were not due to a generalized increase in antibody production in HIV-positive patients because antibody levels against the HA2 antigen of influenza were lower in the HIV patients.




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