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-Herpesvirus Infection1
Trudeau Institute, Saranac Lake, NY 12983
The human 
-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 -herpesvirus-68 has biological
and structural similarities to the human -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 -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 -herpesvirus latency,
and have significant implications for clinical
intervention.
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