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PMID: 16282492 Published · ppublish English Historical Article Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice.

Journal of virology ·Vol. 79 ·No. 23 ·2005-12-00 ·Pages 14933-44

Tumpey TM, García-Sastre A, Taubenberger JK, Palese P, Swayne DE, Pantin-Jackwood MJ, Schultz-Cherry S, Solórzano A, Van Rooijen N, Katz JM, Basler CF

Abstract

The Spanish influenza pandemic of 1918 to 1919 swept the globe and resulted in the deaths of at least 20 million people. The basis of the pulmonary damage and high lethality caused by the 1918 H1N1 influenza virus remains largely unknown. Recombinant influenza viruses bearing the 1918 influenza virus hemagglutinin (HA) and neuraminidase (NA) glycoproteins were rescued in the genetic background of the human A/Texas/36/91 (H1N1) (1918 HA/NA:Tx/91) virus. Pathogenesis experiments revealed that the 1918 HA/NA:Tx/91 virus was lethal for BALB/c mice without the prior adaptation that is usually required for human influenza A H1N1 viruses. The increased mortality of 1918 HA/NA:Tx/91-infected mice was accompanied by (i) increased (>200-fold) viral replication, (ii) greater influx of neutrophils into the lung, (iii) increased numbers of alveolar macrophages (AMs), and (iv) increased protein expression of cytokines and chemokines in lung tissues compared with the levels seen for control Tx/91 virus-infected mice. Because pathological changes in AMs and neutrophil migration correlated with lung inflammation, we assessed the role of these cells in the pathogenesis associated with 1918 HA/NA:Tx/91 virus infection. Neutrophil and/or AM depletion initiated 3 or 5 days after infection did not have a significant effect on the disease outcome following a lethal 1918 HA/NA:Tx/91 virus infection. By contrast, depletion of these cells before a sublethal infection with 1918 HA/NA:Tx/91 virus resulted in uncontrolled virus growth and mortality in mice. In addition, neutrophil and/or AM depletion was associated with decreased expression of cytokines and chemokines. These results indicate that a human influenza H1N1 virus possessing the 1918 HA and NA glycoproteins can induce severe lung inflammation consisting of AMs and neutrophils, which play a role in controlling the replication and spread of 1918 HA/NA:Tx/91 virus after intranasal infection of mice.

MeSH Terms
Animals Disease Models, Animal Hemagglutinin Glycoproteins, Influenza Virus/genetics History, 19th Century Humans Influenza A Virus, H1N1 Subtype/genetics,pathogenicity,physiology Lung/metabolism,pathology,virology Macrophages/immunology,physiology Mice Neuraminidase/genetics Neutrophils/immunology,physiology Orthomyxoviridae Infections/mortality Virus Replication
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Neuraminidase
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Tumpey Terrence M
Influenza Branch, Mail Stop G-16, DVRD, NCID, Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., Atlanta, GA 30333, USA. tft9@cdc.gov
García-Sastre Adolfo
Taubenberger Jeffery K
Palese Peter
Swayne David E
Pantin-Jackwood Mary J
Schultz-Cherry Stacey
Solórzano Alicia
Van Rooijen Nico
Katz Jacqueline M
Basler Christopher F
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.23.14933-14944.2005
Email
tft9@cdc.gov
Published
2005-12-00
Pages
14933-44
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1287592
Subset
IM
Grants
NIAID NIH HHS · P01 AI058113 · United States
NIAID NIH HHS · P01 AI058113-01 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.23.14933-14944.2005 PMC Full Text View journal details
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