TY - JOUR
T1 - Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses
AU - Früh, Klaus
AU - Bartee, Eric
AU - Gouveia, Kristine
AU - Mansouri, Mandana
PY - 2002/9
Y1 - 2002/9
N2 - 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.
AB - 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.
KW - Gamma herpesvirus
KW - Leukemia associated protein
KW - Major histocompatibility
KW - Plant homeo domain
KW - Poxvirus
KW - Ring domain
KW - Ubiquitin
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U2 - 10.1016/S0168-1702(02)00120-X
DO - 10.1016/S0168-1702(02)00120-X
M3 - Review article
C2 - 12297327
AN - SCOPUS:0036711122
SN - 0168-1702
VL - 88
SP - 55
EP - 69
JO - Virus Research
JF - Virus Research
IS - 1-2
ER -