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Crystal Structure of the Cowpox Virus Encoded Protein: Orthopoxvirus MHC Class I-like Protein

Orthopoxviruses can infect a variety of animals, such as rabbits, monkeys, and camels. Four types of orthopoxviruses can also infect humans: variola (smallpox), vaccinia, cowpox, and monkeypox. Data suggest that small rodents may carry cowpox and monkeypox and transmit these infections to people. The number of cowpox and monkeypox cases in humans has increased over the last few decades.

Orthopoxviruses encode a broad arsenal of proteins focused on sabotaging host immunity. Cells infected with cowpox or monkeypox secrete one such protein: orthopoxvirus MHC class I-like protein (OMCP). OMCP can inhibit the host’s natural killer cells (Ref 1) by binding to a molecule on the host cell called NKG2D. OMCP can also limit the activity of other immune cells by interacting with molecules on the host’s T cells and macrophages. Along with natural killer cells, these cells play an important role in antiviral and antitumor immunity.

Researchers from the Center for Structural Genomics of Infectious Diseases (CSGID) at Washington University in St. Louis, Missouri, have determined the 2.25Å-resolution crystal structure of OMCP from cowpox. The structure consists of a truncated MHC class I-like platform domain comprised of a six-stranded beta-sheet flanked with two anti-parallel alpha helices. OMCP is generally similar in structure to host proteins that bind NKG2D.

 

Additionally, OMCP has multiple functions that aid in evading the host immune system. It is capable of binding other host immune receptors, including FcRL5 , a receptor expressed by B-cells (Ref 2). OMCP is the first protein known to bind FcRL5 and suggests an important role for this receptor in host-mediated viral defense.

For more information, please visit the Protein Data Bank entry 4FFE.

orthopox virus structure

References

  • Campbell JA, Trossman DS, Yokoyama WM, Carayannopoulos LN. Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D. J Exp Med. 204, 1311-1317 (2007).
  • Campbell JA et al. Cutting edge: FcR-like 5 on innate B cells is targeted by a poxvirus MHC class I-like immunoevasin. J Immunol. 185, 28-32 (2010).

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Last Updated July 03, 2012

Last Reviewed July 03, 2012