Antibody-mediated control of persistent gamma-herpesvirus infection.
The human gamma-herpesviruses, EBV and Kaposi's sarcoma-associated herpesvirus, establish life-long latency and can reactivate in immunocompromised individuals. T cells play an important role in controlling persistent EBV infection, whereas a role for humoral immunity is less clear. The murine gamma-herpesvirus-68 has biological and structural similarities to the human gamma-herpesviruses, and provides an important in vivo experimental model for dissecting mechanisms of immune control. In the current studies, CD28(-/-) mice were used to address the role of Abs in control of persistent murine gamma-herpesvirus-68 infection. Lytic infection was controlled in the lungs of CD28(-/-) mice, and latency was maintained in B cells at normal frequencies. Although class-switched virus-specific Abs were initially generated in the absence of germinal centers, titers and viral neutralizing activity rapidly waned. T cell depletion in CD28(-/-) mice with compromised Ab responses, but not in control mice with intact Ab responses, resulted in significant recrudescence from latency, both in the spleen and the lung. Recrudescence could be prevented by passive transfer of immune serum. These data directly demonstrate an important contribution of humoral immunity to control of gamma-herpesvirus latency, and have significant implications for clinical intervention.
Kim
In-Jeong
IJ
Trudeau Institute, Saranac Lake, NY 12983, USA.
Flaño
Emilio
E
Woodland
David L
DL
Blackman
Marcia A
MA
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000502:physiology*; D000917:Antibody Formation / Q000235:genetics; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D018106:CD28 Antigens / Q000235:genetics; D005260:Female; D018142:Gammaherpesvirinae / Q000254:growth & development / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D007106:Immune Sera / Q000008:administration & dosage; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D017735:Virus Latency / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D018106:CD28 Antigens; D007106:Immune Sera