The effects of human cytomegalovirus infection on cytoskeleton-associated polysomes

Abstract

Human cytomegalovirus (HCMV) infection induces disruption of the host cell's cytoskeleton (CSK). This disruption is accompanied by three transient phases of actin depolymerization that occur at 20 min, 5 to 10 h and 48 to 72 h post infection (pi). During the 20 min peak of actin depolymerization, the level of cellular polysomes associated with the CSK was reduced, due to release of ribosomes from CSK-associated polysomes. Cellular mRNAs previously existing in these polysomes, however, remained associated with the CSK. Also during this period, nuclear to cytoplasmic transport of host cellular mRNA as well as the association of newly synthesized mRNA with the CSK was temporarily delayed. By 60 min pi, ribosomes, preexisting host cellular mRNA, and newly synthesized mRNAs (host and viral) had reestablished a distribution in the infected cell comparable to that of uninfected cells. Sedimentation profiles of soluble and CSK fractions at various times throughout the viral infection indicated that, although the amount of polysomes associated with the CSK at 20 min pi was reduced, essentially all HCMV and all host cell polysomes present were associated with the CSK. The majority of HCMV DNA hybridizable poly(A)+ RNAs were associated with the CSK throughout the viral infection. These early events appear to correlate with a transient interruption of host cellular mRNA translation early in infection and may represent a process whereby HCMV gene expression becomes competitive with that of the host cell.