Abstract
After herpesviruses encapsidate their genomes in replication compartments (RCs) within the nuclear interior, capsids migrate to the inner nuclear membrane (INM) for nuclear egress. For human cytomegalovirus (HCMV), capsid migration depends at least in part on nuclear myosin Va. It has been reported for certain herpesviruses that the nucleoplasmic subunit of the viral nuclear egress complex (NEC) is important for this migration. To address whether this is true for HCMV, we used mass spectrometry and multiple other methods to investigate associations among the HCMV NEC nucleoplasmic subunit, UL53, myosin Va, major capsid protein, and/or capsids. We also generated complementing cells to derive and test HCMV mutants null for UL53 or the INM NEC subunit, UL50, for their importance for these associations and, using electron microscopy, for intranuclear distribution of capsids. We found modest associations among the proteins tested, which were enhanced in the absence of UL50. However, we found no role for UL53 in the interactions of myosin Va with capsids or the percentage of capsids outside RC-like inclusions in the nucleus. Thus, UL53 associates somewhat with myosin Va and capsids, but, contrary to reports regarding its homologs in other herpesviruses, is not important for migration of capsids towards the INM.
Highlights
Assembled herpesvirus capsids translocate from the nucleus to the cytoplasm in a complicated process known as nuclear egress
Human cytomegalovirus (HCMV), this model is supported for at least some intranuclear capsid migration by data showing that the virus induces the formation of actin filaments in the nucleus that associate with capsids and myosin Va, that treatment with an actin-depolymerizing drug disrupts these filaments and impairs migration to the nuclear rim and nuclear egress, and that siRNA and a nuclear localized dominant negative mutant that antagonize myosin Va impair these processes [6,7]
How nascent herpesvirus capsids migrate from replication compartments (RCs) in the nuclear interior to the periphery during nuclear egress is poorly understood
Summary
Assembled herpesvirus capsids translocate from the nucleus to the cytoplasm in a complicated process known as nuclear egress. As initially proposed for an alphaherpesvirus, herpes simplex virus 1 (HSV-1) [5] capsids move from the nuclear interior towards the nuclear rim by actomyosin-directed transport. Human cytomegalovirus (HCMV), this model is supported for at least some intranuclear capsid migration by data showing that the virus induces the formation of actin filaments in the nucleus that associate with capsids and myosin Va, that treatment with an actin-depolymerizing drug disrupts these filaments and impairs migration to the nuclear rim and nuclear egress, and that siRNA and a nuclear localized dominant negative mutant that antagonize myosin Va impair these processes [6,7]. How the capsid would interact with the actomyosin machinery to be transported from the nuclear interior to the nuclear rim remains unclear
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