Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses

Klaus Früh, Eric Bartee, Kristine Gouveia, Mandana Mansouri

Research output: Contribution to journalReview article

62 Scopus citations

Abstract

Many viruses have developed mechanisms to escape the cellular immune response by inhibiting antigen presentation from major histocompatibility complex (MHC) molecules. Most of these immune escape mechanisms are highly host adapted and specific to a given virus species or family. Recent observations however, suggest that a conserved family of viral proteins is used by both gamma-2 herpesviruses and by poxviruses to downregulate MHC class I. In addition, other cell surface molecules involved in immune recognition by T cells and NK cells are also downregulated. Two open reading frames (ORFs), K3 and K5, of Kaposi's sarcoma associated virus (KSHV) and one ORFs, K3, of murine gamma herpesvirus 68 (MHV68) inhibit surface expression of MHC I molecules. In cells transfected with KSHV-K3 and KSHV-K5, MHC I is rapidly endocytosed and degraded in lysosomes whereas in MHV68-K3 transfected cells, MHC I is targeted for proteasomal degradation. The K3 and K5 genes display a characteristic conserved domain structure of an amino-terminal plant homeo domain/leukemia associated protein-zinc finger domain followed by two carboxyterminal transmembrane domains. Related proteins are not only found in other gamma-2 herpesviruses, but also in several poxviruses. Moreover, recent data suggest that the K3-related protein of myxoma virus also downregulates MHC I. The presence of similar genes in eukaryotic genomes further indicates that the viral ORFs were originally derived from host genes of as yet unknown function. The molecular mechanism of MHC I downregulation by this novel gene family is only poorly understood at present. However, several lines of evidence suggest that they might function as ubiquitin ligases that regulate the intracellular transport of transmembrane proteins through ubiquitination.

Original languageEnglish (US)
Pages (from-to)55-69
Number of pages15
JournalVirus Research
Volume88
Issue number1-2
DOIs
StatePublished - Sep 1 2002

Keywords

  • Gamma herpesvirus
  • Leukemia associated protein
  • Major histocompatibility
  • Plant homeo domain
  • Poxvirus
  • Ring domain
  • Ubiquitin

ASJC Scopus subject areas

  • Cancer Research
  • Virology
  • Infectious Diseases

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