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Characterization of macaque pulmonary fluid proteome during monkeypox infection: dynamics of host response.

TitleCharacterization of macaque pulmonary fluid proteome during monkeypox infection: dynamics of host response.
Publication TypeJournal Article
Year of Publication2010
AuthorsBrown JN, Estep RD, Lopez-Ferrer D, Brewer HM, Clauss TR, Manes NP, O'Connor M, Li H, Adkins JN, Wong SW, Smith RD
JournalMol Cell Proteomics
KeywordsAmino Acid Sequence, Animals, Body Fluids, HeLa Cells, Humans, Lung, Macaca, Molecular Sequence Data, Monkeypox, Polymerase Chain Reaction, Proteome, Tandem Mass Spectrometry, Viral Proteins
Abstract

Understanding viral pathogenesis is challenging because of confounding factors, including nonabrasive access to infected tissues and high abundance of inflammatory mediators that may mask mechanistic details. In diseases such as influenza and smallpox where the primary cause of mortality results from complications in the lung, the characterization of lung fluid offers a unique opportunity to study host-pathogen interactions with minimal effect on infected animals. This investigation characterizes the global proteome response in the pulmonary fluid, bronchoalveolar lavage fluid, of macaques during upper respiratory infection by monkeypox virus (MPXV), a close relative of the causative agent of smallpox, variola virus. These results are compared and contrasted against infections by vaccinia virus (VV), a low pathogenic relative of MPXV, and with extracellular fluid from MPXV-infected HeLa cells. To identify changes in the pulmonary protein compartment, macaque lung fluid was sampled twice prior to infection, serving as base line, and up to six times following intrabronchial infection with either MPXV or VV. Increased expression of inflammatory proteins was observed in response to both viruses. Although the increased expression resolved for a subset of proteins, such as C-reactive protein, S100A8, and S100A9, high expression levels persisted for other proteins, including vitamin D-binding protein and fibrinogen γ. Structural and metabolic proteins were substantially decreased in lung fluid exclusively during MPXV and not VV infection. Decreases in structural and metabolic proteins were similarly observed in the extracellular fluid of MPXV-infected HeLa cells. Results from this study suggest that the host inflammatory response may not be the only facilitator of viral pathogenesis, but rather maintaining pulmonary structural integrity could be a key factor influencing disease progression and mortality.

DOI10.1074/mcp.M110.001875
Alternate JournalMol. Cell Proteomics
PubMed ID20736407
PubMed Central IDPMC3101861
Grant ListP41 RR018522 / RR / NCRR NIH HHS / United States
P41 RR018522-08 / RR / NCRR NIH HHS / United States
RR00163 / RR / NCRR NIH HHS / United States
RR18522 / RR / NCRR NIH HHS / United States
Y1-AI-4894-01 / AI / NIAID NIH HHS / United States
Y1-AI-8401 / AI / NIAID NIH HHS / United States
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