Induction of proliferating cell nuclear antigen and Ki-67 expression by cytomegalovirus infection

With the goal of facilitating viral reproduction, cytomegalovirus (CMV) induces changes in the host cell replication machinery. Very little information is available, however, on the effects brought about by CMV on proliferating cell nuclear antigen (PCNA) and Ki-67 expression in infected cells. Fifty-five paraffin-embedded tissue samples (43 gastrointestinal, 10 skin, and 2 kidney biopsies) with both histological and immunohistochemical evidence of CMV infection were investigated for PCNA and Ki-67 expression by the avidinbiotin-peroxidase method. Of the 55 cases studied, 47 were positive for PCNA and 46 for Ki-67. PCNA and Ki-67 immunostaining was more striking in CMV-immunoreactive, inclusion-free cell nuclei, whereas cell nuclei exhibiting well-developed CMV inclusions either showed a weak peripheral signal for both proliferation markers, or were completely negative. Enhanced PCNA and Ki-67 expression appears to be among the changes induced by CMV infection in host cells. Moreover, this induction seems to reach its peak during the earlier phases of CMV infection and abate as the infection proceeds to its inclusion-forming phases, when a sufficiently high viral load would have been attained.