A human cytomegalovirus function inhibits replication of herpes simplex virus

Abstract

Human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of herpes simplex virus type 1 (HSV-1). A delay in HSV replication of 15 h as well as a consistent, almost 3 log inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 h after superinfection were observed compared with controls infected with HSV alone. Treatment of HCMV-infected HEL cells with cycloheximide (100 ,ug/mI) for 3 or 24 h, conditions known to result in accumulation of HCMV immediate-early and early mRNA, was demonstrated effective in blocking HCMV protein synthesis, as shown by immunoprecipitation with HCMV antibody-positive polyvalent serum. Cycloheximide treatment of HCMV-infected HEL cells and removal of the cycloheximide block before superinfection inhibited HSV-1 replication more efficiently than non-drug-treated superinfected controls. HCMV DNA-negative temperature-sensitive mutants restricted HSV as efficiently as wild-type HCMV suggesting that immediate-early and/or early events which occur before viral DNA synthesis are sufficient for inhibition of HSV. Inhibition of HSV-1 in HCMV-infected HEL cells was unaffected by elevated temperature (40.5°C). However, prior UV irradiation of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HSV-2 replication was similarly inhibited in HCMV-infected HEL cells. However, replication of adenovirus, another DNA virus, was not restricted in these cells under the same conditions. Superinfection of HCMV-infected HEL cells with HSV-1 labeled with [3H]thymidine provided evidence that the labeled virus could penetrate to the nucleus of cells after superinfection. Evidence for penetration of superinfecting HSV into HCMV-infected cells was also provided by blot hybridization of HSV DNA synthesized in cells infected with HSV alone versus superinfected cell cultures at 0 and 48 h after superinfection. In addition, superinfection with vesicular stomatitis virus ruled out a role for interferon in restriction of HSV replication in this system.

Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses

“…HIV results, coupled with the observation that inhibition occurs dotype alone; M, as early as 8 h after HCMV infection, suggest that an HCMV plus HCMV; A, early protein is central to this process. Our findings are consistent with those of Cockley et al (13), who found that HCMV can inhibit the replication of HSV-1 and HSV-2 but 3) pseudotypes not adenovirus or vesicular stomatitis virus in human emof HIV by the bryonic lung cells. That communication also reported that vas the same in UV irradiation of the HCMV particles prevented the inhibisuggesting that tion of HSV replication from occurring and that viral DNA ry for inhibition synthesis was not necessary for this shutoff.…”

Viral interference between low pathogenic avian influenza H9N2 and avian infectious bronchitis viruses in vitro and in ovo

“…It is well known that various viral super-infection interferences do occur at the cellular level, in vitro, as it has been reported for the occurrence of AIV-New Castle Disease Virus, Hepatitis B Virus-Hepatitis C virus and AIV-IBV interferences (Banfield et al, 2003;Christen et al, 1990;Cockley et al, 1988), showing that the pre-inoculated virus always induces a lower growth of the super-infecting virus (Sonnenfeld and Merigan, 1979). In fact, viral interference may be broadly classified in two categories relating to either attachment or intracellular virus interactions.…”

“…Initiation of super-infection inhibition was described for many bacteria, plants and animal viruses (Christen et al, 1990;Cockley et al, 1988). Although AIV and IBV are the causative agents of two major avian diseases, unfortunately, little is known about their interactions when co-infecting chicken hosts.…”

Case Report: Persistent cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation using in vivo alemtuzumab: emergence of resistant CMV due to mutations in the UL97 and UL54 genes

“…The susceptibilities of the CMV isolate to ganciclovir, cidofovir, and foscarnet were examined by the plaque reduction assay [Cockley et al, 1988;Shiraki et al, 1990Shiraki et al, , 1991aYukawa et al, 1996]. Briefly, all assays were carried out in confluent HEL cell monolayers in 60 mm plastic dishes.…”