Beta interferon production in primed and unprimed cells infected with human cytomegalovirus

Abstract

Human cytomegalovirus induced beta interferon in cultures of human foreskin cells. The inhibitor was first released between 8 and 16 hours after infection, about 48 hours before progeny virus. In cultures infected with low concentrations of virus, interferon was produced as the infection spread, and then in amounts larger than expected. After infection with cytomegalovirus, cells which had been primed for 48 hours with purified beta interferon produced significantly more interferon than unprimed cells, and the interferon was produced earlier, between 2 and 8 hours after infection. CMV-induced interferon also was able to prime cells. The data suggest that the relatively large quantities of interferon detected in cultures infected with low concentrations of cytomegalovirus result from endogenous priming: those cells infected early first produce interferon which primes uninfected cells, then virus which induces the primed cells to produce interferon in relatively high concentrations.

Major Human Cytomegalovirus Structural Protein pp65 (ppUL83) Prevents Interferon Response Factor 3 Activation in the Interferon Response

“…RVAd65 and AD169varDE infected Ͼ98% of cells at an MOI of 4. Virus-free infected cell supernatants (wt or mutant-infected) collected at 4 or 6 h postinfection (hpi) after exposure to a high MOI inoculum failed to induce cellular gene expression or to interfere with replication of vesicular stomatitis virus (data not shown), consistent with previous observations (55). IFN-␤ is induced between 8 and 16 hpi at low MOIs with CMV (9, 55) but is not induced under high MOI conditions.…”

“…A virion-or virion glycoprotein-mediated activation of this IFN-like response is controlled through NF-B (76)(77)(78) and may benefit viral infection, given the distribution of NF-B sites on the viral genome (43). IFN-␤ gene transcription is induced by this IFN-like response in CMV-infected cells; however, IFN-␤ is only produced at low levels by infected cell cultures exposed to low multiplicities of infection (MOIs) (9,55). IFN-␤ has not been detected in culture supernatants or virus preparations after infection at high MOIs or in purified virus stocks prepared by using low MOIs (references 41 and 81 and this report).…”

“…Activation of IRF-3 only occurs in mutant virus-infected cells at late times after infection, although the activation of IRF-3 responsive genes does not apparently suppress mutant virus replication (59). CMV may have a posttranscriptional mechanism to prevent full expression of IFN-␤ (13, 81) that may become partially compromised at low MOI (55). CMV is generally able to blunt the antiviral effects of IFN-␣/␤ when applied exogenously so long as the virus is used at MOI that lead to uniform infection (29,41,47), and two gene products that block protein kinase R activity are known (14) to contribute to this resistance.…”

The role of interferon ? in human cytomegalovirus-mediated inhibition of HLA DR induction on endothelial cells

“…HCMV, which has a large, linear double-stranded DNA molecule, induces IFNI3 synthesis in fibroblasts eight to 16h post-infection [2,38]. There are no reports that human ECs produce IFNI3 or IFN~ following infection with HCMV [44]; however, human ECs are capable of synthesizing IFNI3 in response to infection with Newcastle disease virus, Sendai virus, vesicular stomatitis virus and poly(I):poly(C) [11].…”

Xiao Chai Hu Tang inhibits CVB1 virus infection of CCFS-1 cells through the induction of Type I interferon expression

“…The Type II IFN consists the IFN-γ gene and is induced directly by virus infection. It is synthesized in response to the recognition of infected cells by activated T lymphocytes and natural killer (NK) cells [65,66].…”