Abstract
CD8 T cells are recognized key players in control of persistent virus infections, but increasing evidence suggests that assistance from other immune mediators is also needed. Here, we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus (LCMV), a prototypic mouse model of systemic persistent infection. Mice expressing transgenic B cell receptors of LCMV-unrelated specificity, and mice unable to produce soluble immunoglobulin M (IgM) exhibited protracted viremia or failed to resolve LCMV. Virus control depended on immunoglobulin class switch, but neither on complement cascades nor on Fc receptor γ chain or Fc γ receptor IIB. Cessation of viremia concurred with the emergence of viral envelope-specific antibodies, rather than with neutralizing serum activity, and even early nonneutralizing IgM impeded viral persistence. This important role for virus-specific antibodies may be similarly underappreciated in other primarily T cell–controlled infections such as HIV and hepatitis C virus, and we suggest this contribution of antibodies be given consideration in future strategies for vaccination and immunotherapy.
Highlights
Infections associated with persistent viremia include human immunodeficiency virus (HIV) and the hepatitis B and C viruses (HBV, hepatitis C virus (HCV)), which affect more than 500 million people worldwide
Declining viremia in HIV coincides with the appearance of antiviral CD8 T cells [6,7], and the concept of cytotoxic T lymphocyte (CTL)-mediated HIV control was further strengthened by the association of ‘‘protective’’ HLA molecules with long-term nonprogression in many so-called ‘‘elite controllers’’ [8]
Recent attempts at vaccinating against HIV have relied on the induction of specific antiviral killer T lymphocytes but have failed to confer protection on the host
Summary
Infections associated with persistent viremia include human immunodeficiency virus (HIV) and the hepatitis B and C viruses (HBV, HCV), which affect more than 500 million people worldwide. The key role of CTL in controlling and resolving systemic persistent infections has initially been described for LCMV [3,4,5] with subsequent extension of the concept to important human pathogens such as HIV and HCV. Declining viremia in HIV coincides with the appearance of antiviral CD8 T cells [6,7], and the concept of CTL-mediated HIV control was further strengthened by the association of ‘‘protective’’ HLA molecules with long-term nonprogression in many so-called ‘‘elite controllers’’ [8]. Analogous observations were made in HBV- and HCV-infected monkeys [12,13]
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