A new mechanism by which human immunodeficiency virus (HIV) cripples immune responses in virus-infected AIDS patients is reported in the March issue of Nature Immunology. HIV Nef protein blocks critical signaling pathways in B cells, disrupting their ability to make effective neutralizing antibodies to the virus.
Andrea Cerutti and colleagues show Nef protein released by infected cells can prevent B cells from undergoing a full maturation process called antibody class switch recombination (CSR). CSR tailors antibody responses to best counter the offending pathogen e.g. CSR is required to make antibodies that can cross mucosal borders to inhibit viruses present in body secretions. Nef alone was sufficient to disrupt CSR by activating natural inhibitors of this process in B cells. Although B cells could still secrete an immature type of antibody, called IgM, these antibodies are not nearly as effective at clearing pathogens throughout the body and especially at mucosal surfaces, which are the primary sites of viral entry.
These data help to explain why anti-viral antibody immune responses are so poor, even at early times after infection when patients T cell counts are still high enough to trigger antibody production. Countering this Nef-induced inhibition might help to stem HIV early in infection.
Andrea Cerutti (Weill Medical College of Cornell University, NY, USA)
Abstract available online.
(C) Nature Immunology press release.
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