Host-Dependent Restriction of Mengovirus Replication

Abstract

Mengovirus infection of a restrictive cell line, Maden's bovine kidney (MDBK), results in a virus yield 1,000-fold less than that obtained from productively infected cell lines such as L cells or Ehrlich ascites tumor cells (EAT). Cells of both types of host systems are infected with comparable efficiencies and are completely killed as a consequence of infection. Infective center assays, coupled with the observation of total cell killing, suggest that comparable numbers of cells synthesize viral antigen and release virus in both types of host system. Viral-specific ribonucleic acid (RNA) synthesis is initiated and proceeds in an identical fashion for approximately 4 hr after the infection of MDBK, EAT, or L-cells. At this time, viral RNA synthesis in MDBK ceases, whereas viral RNA synthesis in EAT and L-cells continues at a linear rate. These results indicate that none of the early viral events leading to the initiation of viral-specific RNA synthesis constitutes the primary site of mengovirus restriction in MDBK. Rather it appears that the cessation of viral RNA synthesis in restrictive cells constitutes the primary limiting event. Based on its delayed interaction with mengovirus RNA synthesis, it appears that the host-related restrictive agent is initially compartmentalized and then released as a consequence of infection subsequent to those early events in mengovirus infection leading to the initiation and continued synthesis of viral RNA.

Host-dependent restriction of mengovirus replication. II. Effect of host restriction on late viral RNA synthesis and viral maturation

“…Additional experiments confirmed (23,24) that mengovirus infection of restrictive MDBK cells does proceed in a normal fashion for the first several hours of the virus replicative cycle.…”

“…Because mengovirus-infected HeLa cells were used as the permissive host in this study, rather than L cells (4,23,24), several control experiments were run to confirm that mengo infection of HeLa cells was similar to that in L cells.…”

“…Mengovirus propagation and purification. Mengovirus was routinely propagated on L cell monolayers as previously described (23), except that the incubation period was extended to 24 h.…”

“…Prather, Ph.D. thesis, Indiana Univ., Bloomington, Ind., 1974; 4, 23). The mengovirus restriction phenomenon observed in MDBK cells does not appear to result from an absence of mengospecific receptor sites on the cell surface, as the infective process proceeded for the first 4 h of the viral replicative cycle in a normal fashion (4,23,24). Additionally, mengovirus-infected MDBK cells show a pattern of cytopathogenicity similar to productively infected cells (23).…”

“…Wall and Taylor (23,24) investigated the restricted replication of mengovirus in MDBK cells, with particular attention to the synthesis and accumulation of virus-specific RNA in the nonpermissive host when compared with the same in permissive Erlich ascites tumor and L cells. They reported that radioactive uridine I Present address: Department of Microbiology, College of Medicine, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pa. 17033. accumulation into acid-insoluble material ceased prematurely at 4 h after infection in the inefficiently infected MDBK cells (25), and that the amount of mengovirus-specific RNA was about fourfold less than that accumulated in productively infected L cells (24).…”