DEVELOPMENTALLY-REGULATED HERPESVIRUS PLAQUE-FORMATION IN ARTERIAL SMOOTH-MUSCLE CELLS

Previous studies of age-related susceptibility to viral infection have focused largely on the effects of aging on the immune response. Littl e attention has been given to age-related changes in the infectivity o f target cells. We show here a fourfold greater plating efficiency of herpes simplex virus type 1 (HSV-1) for cultured vascular smooth muscl e cells derived from adult rats compared with cells from genetically i dentical pup rats. The difference in plating efficiency appeared to be due to differences in initial attachment of the virion to the cell su rface. There were no differences in the rate of viral entry or the eff iciency of viral replication at high multiplicities of infection and n o resistant ''subpopulation'' of pup cells. The pup cells did not rele ase a soluble inhibitor of infection. Infection in both cell types was inhibited similarly by basic fibroblast growth factor (bFGF). Althoug h adult cells exhibited a more vigorous mitogenic response to bFGF tha n did pup cells, binding studies did not demonstrate significant diffe rences in the binding of bFGF to the cell surface, suggesting that dif ferential expression of high-affinity FGF receptors could not be corre lated with the difference in infectivity. We speculate that difference s in the distribution of heparan sulfate in the cell surface, which se rves as the initial attachment site for HSV-1, may explain the observe d differences in plating efficiency. Since age is a risk factor for th e development of atherosclerosis, these results have potential implica tions for susceptibility of the vasculature to herpesviral infections as a function of the development of the vessel wall.