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Vaccinia Virus Infection & Temporal Analysis of Virus Gene Expression: Part 1
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Elucidating the role of the complement control protein in monkeypox pathogenicity.

Paul N Hudson1, Joshua Self, Sonja Weiss

  • 1Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases and Biotechnology Core Facility Branch, Division of Safety Research, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. fst6@cdc.gov

Plos One
|April 13, 2012
PubMed
Summary

Monkeypox virus (MPXV) virulence differs between clades due to a complement control protein (CCP). Removing CCP reduced MPXV disease severity, but it

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Area of Science:

  • Virology
  • Immunology
  • Pathogenesis

Background:

  • Monkeypox virus (MPXV) causes a smallpox-like illness.
  • Distinct MPXV clades (West African and Congo Basin) exhibit varying pathogenicity.
  • Genomic analysis revealed a deletion in West African MPXV strains, lacking a complement control protein (CCP) gene.

Purpose of the Study:

  • To investigate the role of MPXV complement control protein (CCP) in MPXV virulence and pathogenesis.
  • To determine if CCP is solely responsible for the increased virulence of the Congo Basin clade.

Main Methods:

  • MPXV CCP gene was incorporated into the West African strain and removed from the Congo Basin strain using homologous recombination.
  • Wild type and recombinant MPXV strains were characterized for CCP expression and activity.
  • Prairie dogs were intranasally infected to monitor disease progression and viral load.

Main Results:

  • Removal of CCP from the Congo Basin strain decreased MPXV disease morbidity and mortality, without significantly affecting viral load.
  • Inclusion of CCP in the West African strain altered disease manifestation but not mortality.
  • CCP was confirmed as an important immunomodulatory protein in MPXV pathogenesis.

Conclusions:

  • CCP plays a significant role in MPXV pathogenesis and virulence.
  • CCP is not the sole factor driving the increased virulence of the Congo Basin MPXV clade.