Rabbit kidney cells abortively infected with human cytomegalovirus are arrested in mitotic phase

Summary In rabbit kidney epithelial cells (RK₁₃) abortively infected with human cytomegalovirus (HCMV), DNA synthesis at 1 or 2 days post-infection was enhanced 4 to 5 fold, compared to mock-infected cells. DNA analysis by isopycnic centrifugation revealed that the DNA newly synthesized in the virus infected RK₁₃ cells was of cellular origin. HCMV infection also caused a marked increase in the mitotic activity of RK₁₃ cells. When semi-confluent RK₁₃ cells were infected more than 20 per cent of cells demonstrated mitosis at 72 hours post-infection although the rate of cell growth was considerably reduced compared to that of uninfected cells. The most frequent chromosomal change observed was fragmentation although other aberrations, gap, break, deletion etc. occurred also.Two immediate-early viral polypeptides with apparent molecular weights 72,000 (72K) and 76,000 (76K) daltons were produced in both RK₁₃ cells and human embryonic lung cells (HEL) by 3 hours post-infection. Synthesis of the 76K polypeptide was greater than that of the 72K polypeptide in non-permissive RK₁₃ cells whereas the reverse occurred in permissive HEL cells. Furthermore, of three early polypeptides which were expressed in productively infected HEL cells two, 88K and 80K, were not detected in abortively infected RK₁₃ cells.These results suggest that the arrest in mitosis of the abortively infected RK₁₃ cells and the subsequent chromosomal changes are associated with the altered expression of immediate-early or early virus functions in these cells.Following HCMV infection permissive HEL cells undergo a characteristic sequence of morphological changes (3) of which cell rounding and contraction are observed in the early stages and could be related to either the action of cellular contractile proteins or changes in the plasma membrane permeability and a concomitant Ca⁺⁺ influx (2). Relaxation and cell enlargement are other changes considered to be initiated by early virus functions although they occur after the commencement of virus DNA synthesis. Thus, the expression of immediate-early and early virus functions has an important role in controlling the sequential morphological changes in infected cells and may also be important in determining whether infection with HCMV will be productive or abortive.With 4 Figures