Increased immunoglobulin G, but not M, binding to endogenous retroviral antigens in HIV-1 infected persons

The modes of interaction between products of human endogenous retroviral (HERV) sequences and the immune system are largely unknown. In HIV infected persons, an exogenous retrovirus adds further complexity to the situation. Therefore, 14 synthetic peptides with sequences derived from conserved regions of various endogenous retroviruses (ERVs) and from related exogenous retroviruses were used to search for IgG and IgM antibodies that bind to such antigens in 15 HIV-1 seropositive and 17 seronegative immunosuppressed patients. IgG binding to three peptides, namely, the C-terminal half of murine leukemia virus (MLV) capsid protein, the conserved portion of HERV-H transmembrane protein, and the Pol region of human mouse mammary tumor virus (MMTV)-like (HML3) sequence, was observed in both groups. Binding was, however, more frequent and more firm in HIV-1 positive samples (P<0.0001, Wilcoxon rank sum test). IgM binding to the same peptides showed no significant differentiation between the two groups of patients. Binding to both immunoglobulin isotypes was sometimes variable over time in both groups. No correlation of either IgG or IgM peptide binding with progression to AIDS in HIV-1 infected individuals was observed. Inhibition studies using analogous endogenous and exogenous retroviral peptides, including HIV-1, demonstrated specificity of the IgG antibodies for a narrow range of MLV- and MMTV-like retroviral antigens, and excluded cross-reactivity of antibodies to HIV-1 as a cause of these observations. Thus, unlike IgG, IgM binding to retroviral antigens was ubiquitous. It is suggested that anti-HERV IgM belong to a class of natural antibodies and might serve as primers in the mediation of humoral immune responses to more or less related exogenous retroviruses. Increased IgG binding in HIV-1 infected individuals could result from such priming, or reflect higher HERV antigen expression.