Selection of HSV capsids for envelopment involves interaction between capsid surface components pUL31, pUL17, and pUL25.

During egress from the nucleus, HSV capsids that contain DNA (termed C capsids) are preferentially enveloped at the inner nuclear membrane over capsid types lacking DNA. Using coimmunoprecipitation and biochemical analyses of wild-type and mutant capsids, we identify an interaction between a complex of pU(L)17/pU(L)25, termed the C capsid-specific complex (CCSC), and pU(L)31, a component of the nuclear egress complex (NEC). We also show that the interactions between these components are dependent on expression of all three proteins but occur independently of the pU(L)31 interacting protein and NEC component pU(L)34, as well as a kinase encoded by U(S)3 that phosphorylates both pU(L)31 and pU(L)34. The interaction between the CCSC and pU(L)31 in the NEC suggests a mechanism to conserve viral resources by promoting assembly of only those viral particles with the potential to become infectious.