Human cytomegalovirus decreases constitutive transcription of MHC class II genes in mature Langerhans cells by reducing CIITA transcript levels (154.32)

Abstract

Abstract Human cytomegalovirus (HCMV) productively infects CD34+ progenitor-derived, mature Langerhans-type dendritic cells (matLC) and reduces surface expression of MHC class II complexes (MHC II) by increasing intracellular retention of these molecules. To determine whether HCMV inhibits MHC II expression by other mechanisms, we assessed mRNA levels of the class II transcriptional regulator, CIITA, and several of its target genes in infected matLC. CIITA mRNA levels were significantly lower in HCMV-infected matLC than in mock-infected cells. Analysis of promoter-specific CIITA isoforms revealed that types I, III and IV were decreased by HCMV, a result not seen after incubation of matLC with LPS. Exposure to UV-inactivated virus failed to reduce CIITA mRNA levels, implicating de novo viral gene expression in this effect. The stability of CIITA mRNA was not diminished by HCMV, arguing that diminished transcription is the mechanism for CIITA mRNA reduction. HCMV-infected matLC expressed lower levels of DR transcripts and reduced DR protein synthesis rates compared to mock-infected matLC. Thus, we demonstrate that HCMV infection of a human dendritic cell subset inhibits constitutive CIITA expression, resulting in reduced MHC II biosynthesis as a candidate immunoevasive mechanism.