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

Abstract

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.

Absence of XMRV in Peripheral Blood Mononuclear Cells of ARV-Treatment Naïve HIV-1 Infected and HIV-1/HCV Coinfected Individuals and Blood Donors

“…Human IgG reactivity to MLV capsid has been reported previously [59], [60]. In one study, a higher frequency of individuals with MLV capsid-reactive IgG was seen with HIV-1 infection compared to HIV-1 negative controls, a trend we did not observe with this cohort [59]. Nonetheless, proteins encoded by HERVs represent a potential source of antigen that may give rise to antibodies that are cross-reactive with XMRV.…”

“…It is possible that the positive signals obtained in our immunoblots are due to the presence of cross-reactive antibodies to proteins encoded by human endogenous retroviruses (HERVs), a large group of which is similar to MLVs [57], [58]. Human IgG reactivity to MLV capsid has been reported previously [59], [60]. In one study, a higher frequency of individuals with MLV capsid-reactive IgG was seen with HIV-1 infection compared to HIV-1 negative controls, a trend we did not observe with this cohort [59].…”

HIV infection and HERV expression: a review

“…Fourteen peptides derived from various endogenous retroviruses were used to search for IgM and IgG antibodies in HIV-1 infected and uninfected immunosuppressed persons by Lawoko et al . [78]. Three peptides, corresponding to the C-terminal half of the murine leukaemia virus capsid protein, a conserved domain of the HERV-H transmembrane domain, and part of HERV-K HML-3 encoded Pol, were found to bind IgG in both groups, with stronger binding of the latter two peptides in HIV-1 infected patients [78].…”

Activation of LTRs from Different Human Endogenous Retrovirus (HERV) Families by the HTLV-1 Tax Protein and T-Cell Activators

“…HSV-1 and the influenza virus have been shown to modulate LTR activity of HERV-W while HERV-K LTR activity was positively modulated by the influenza A/WSN/44 strain [19–21]. A number of studies have also highlighted an increase in the expression of mostly HERV-K family members in HIV-1-infected patients, thereby leading to a CTL response toward HERV proteins [28–30]. An in vitro study has further shown that HIV infection leads to increase in HERV-K expression [31].…”