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KSHV-K5 inhibits phosphorylation of the major histocompatibility complex class I cytoplasmic tail

E Paulson1, C Tran, K Collins

  • 1The R. W. Johnson Pharmaceutical Research Institute, 3210 Merryfield Row, San Diego, California 92121, USA.

Virology
|October 17, 2001
PubMed

Insights

Kaposi's sarcoma-associated herpesvirus (KSHV) proteins K3 and K5 internalize major histocompatibility complex class I (MHC I) molecules. This process does not require MHC I phosphorylation, indicating a distinct viral immune evasion mechanism.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Major histocompatibility complex class I (MHC I) molecules present antigens to T cells, crucial for immune surveillance.
  • Kaposi's sarcoma-associated herpesvirus (KSHV) proteins K3 and K5 are known to downregulate MHC I.
  • Intracellular trafficking of MHC I is influenced by its cytoplasmic tail, including phosphorylation sites.

Purpose of the Study:

  • To investigate the role of MHC I phosphorylation in KSHV K3 and K5-mediated internalization.
  • To elucidate the molecular mechanisms by which K3 and K5 downregulate MHC I.
  • To compare the MHC I downregulation mechanisms of K3 and K5 with other viral proteins like HIV nef.

Main Methods:

  • Utilized in vivo labeling experiments to assess MHC I phosphorylation.
  • Employed deletion and mutation studies of the MHC I tail.
  • Analyzed the effect of KSHV K3 and K5 proteins, including mutated K5 variants, on MHC I expression and trafficking.

Main Results:

  • KSHV K3 and K5 proteins mediate the internalization of MHC I molecules.
  • MHC I phosphorylation was found to be inhibited in K5-transfected cells, but this inhibition did not cause internalization.
  • Both K3 and K5 could downregulate MHC I even when conserved phosphorylation sites were absent, suggesting phosphorylation is not the cause.
  • Minimal MHC I tail sequences required for downregulation differed between K3, K5, and HIV nef.

Conclusions:

  • KSHV K3 and K5 downregulate MHC I through a mechanism distinct from other viral immune evasion strategies.
  • Inhibition of MHC I phosphorylation by K5 is a consequence, not a cause, of MHC I internalization.
  • The carboxy-terminal region of MHC I is essential for K3 and K5-mediated internalization, but the specific requirements vary between these viral proteins.

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