Enhanced Antibody Responses to Epstein-Barr Virus in HIV-Infected Homosexual Men

Abstract

We investigated the association between human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infections in 593 homosexual men. The status of EBV infection in this group was evaluated based on serological evidence of EBV-specific antibody responses. The geometric mean titers (GMT) of antibody to EBV capsid antigen (EBV-VCA) (1:154) and EBV early antigen (EA) (1:16) in 141 HIV-seropositive men were significantly higher than respective titers in 452 HIV seronegative men (1:95 and 1:12). Antibody titers to EBV were higher in HIV-infected men with lymphadenopathy than in asymptomatic HIV-seropositive men. However, these correlation were less evident in patients with AIDS-related complex. Elevated antibody titers to EBV were found to be independent of levels of total serum IgG. Cytomegalovirus (CMV) antibody titers were also found to be significantly increased among HIV-seropositive men, independent of total IgG. Antibody titers to EBV were not correlated with those to CMV in either HIV-seronegative or HIV-seropositive men. Subjects without evidence of HIV infection, but who had high antibody titers to EBV-VCA and EBV-EA, had elevated mean numbers of CD3+, CD4+, and CD8+ cells, and lower levels of CD4+/CD8+ cell ratios compared to subjects with low EBV-antibody titers. This study suggests that the elevated levels of circulating antibodies against EBV in homosexual men are associated with loss of control of latent EBV due to HIV infection.

CD8+Cytotoxic T Lymphocyte Responses to Lytic Proteins of Human Herpes Virus 8 in Human Immunodeficiency Virus Type 1–Infected and –Uninfected Individuals

“…Possible reasons for the predominant CTL activity to gH during HIV-1 infection include cross-reactivity to non-HHV-8 antigens, such as the EBV homologue of gH. Indeed, EBV infection is active in a large proportion of HIV-1-infected individuals, as shown by persistent shedding of the virus and high titers of antibodies to EBV [12,13]. However, this is unlikely to be the cause of the anti-HHV-8 CTL activity detected in our study, because we have shown in longitudinal studies that CD8 ϩ T cell responses to these HHV-8 lytic proteins are not due to cross-recognition by T cells Alternatively, this more robust anti-gH T cell reactivity could be related to selective production or more dominant immunogenicity of this lytic protein during persistent HIV-1 infection, with consequent differential T cell reactivity that is suppressed at higher HIV-1 loads.…”

Sequential serological studies of homosexual men with and without HIV infection. Epstein-Barr virus activation preceding and following HIV seroconversion

“…However, increased IgA responses after seroconversion may be part of HIV-related B cell changes and thus should be interpreted with caution. Activation of both EBV and CMV following HIV infection has already been noted by others and may be due to both direct effects (Lai, Li & Volsky, 1989) and to the HIVrelated profound defect in cellular immunity which is important in controlling latent herpes virus infections (Birx, Redfield & Tosato, 1986;Rahman et al, 1989;Rinaldo, 1990). There is strong experimental evidence (Gendelman et al, 1986;Pagano et al, 1988;Skolnik et al, 1988;Albrecht et al, 1989;Clouse et al, 1989) and some clinical observations suggesting that activated EBV or CMV infections may be associated with enhanced replication of pre-existing HIV and accelerated progression to AIDS, but this cannot be inferred from our series.…”

Evidence of an in vitro association between human immunodeficiency virus antigen P24 and Epstein-Barr virus DNA

“…This could be the result of specific cell-to-cell interactions enhanced by the in vitro conditions. It is a well-known fact that HIV-infected people have a uniformly deftcient virus-specific cytotoxic lymphocyte function, and specifically present serious impairment in T-cell suppression of EBV-infected B-cells (5); in consequence, the number of circulating infected lymphocytes is abnormally high in these individuals (6,12). Therefore, there is an increased probability that a progressive proliferation of these cells occurs when cultured in vitro.…”