The natural killer (NK) cell activation receptor Ly49H is required for resi
stance to murine cytomegalovirus (MCMV). We show here that NK cell prolifer
ation and production of interferon-gamma (IFN-gamma) was not dependent on L
y49H expression during early MCMV infection. During a later phase of infect
ion, however, Ly49H(+) NK cells selectively proliferated and this expansion
was blocked by anti-Ly49H administration. With vaccinia virus infection, n
either the early nor late phase of NK cell proliferation was selective for
Ly49H(+) NK cells. These findings indicated that Ly49H(+) NK cells were spe
cifically activated by MCMV and that MCMV infection was characterized by no
nspecific and specific phases of NK cell activation in vivo.