title: Elimination of A-type inclusion formation enhances cowpox virus replication in mice: implications for orthopoxvirus evolution.
abstract: Some orthopoxviruses including cowpox virus embed virus particles in dense bodies, comprised of the A-type inclusion (ATI) protein, which may provide long-term environmental protection. This strategy could be beneficial if the host population is sparse or spread is inefficient or indirect. However, the formation of ATI may be neutral or disadvantageous for orthopoxviruses that rely on direct respiratory spread. Disrupted ATI open reading frames in orthopoxviruses such as variola virus, the agent of smallpox, and monkeypox virus suggests that loss of this feature provided positive selection. To test this hypothesis, we constructed cowpox virus mutants with deletion of the ATI gene or another gene required for embedding virions. The ATI deletion mutant caused greater weight loss and higher replication in the respiratory tract than control viruses, supporting our hypothesis. Deletion of the gene for embedding virions had a lesser effect, possibly due to known additional functions of the encoded protein.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3210, Bethesda, MD 20892-3210, USA.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Kastenmayer
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3210, Bethesda, MD 20892-3210, USA.
authors.forename: Liliana
authors.initials: L
authors.lastname: Maruri-Avidal
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3210, Bethesda, MD 20892-3210, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Americo
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3210, Bethesda, MD 20892-3210, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3210, Bethesda, MD 20892-3210, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Weisberg
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, MSC 3210, Bethesda, MD 20892-3210, USA. Electronic address: bmoss@nih.gov.
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015605:Cowpox / Q000821:virology*; D015608:Cowpox virus / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D006801:Humans; D007181:Inclusion Bodies, Viral / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018155:Orthopoxvirus / Q000235:genetics* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014764:Viral Proteins
keywords: Cowpox virus inclusions; Poxvirus pathogenicity; Respiratory virus infection