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Journal of Virology, September 2008, p. 8560-8569, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00699-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

T Lymphocytes Contribute to Antiviral Immunity and Pathogenesis in Experimental Human Metapneumovirus Infection{triangledown}

Deepthi Kolli,1,{dagger} Efthalia L. Bataki,1,{dagger} LeAnne Spetch,1 Antonieta Guerrero-Plata,1 Alan M. Jewell,4 Pedro A. Piedra,4 Gregg N. Milligan,1,2,3 Roberto P. Garofalo,1,2,3 and Antonella Casola1,2,3*

Departments of Pediatrics,1 Microbiology and Immunology,2 Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston,3 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas4

Received 28 March 2008/ Accepted 10 June 2008

Human metapneumovirus (hMPV), a member of the family Paramyxoviridae, is a leading cause of lower respiratory tract infections in children, the elderly, and immunocompromised patients. Virus- and host-specific mechanisms of pathogenesis and immune protection are not fully understood. By an intranasal inoculation model, we show that hMPV-infected BALB/c mice developed clinical disease, including airway obstruction and hyperresponsiveness (AHR), along with histopathologic evidence of lung inflammation and viral replication. hMPV infection protected mice against subsequent viral challenge, as demonstrated by undetectable viral titers, lack of body weight loss, and a significant reduction in the level of lung inflammation. No cross-protection with other paramyxoviruses, such as respiratory syncytial virus, was observed. T-lymphocyte depletion studies showed that CD4+ and CD8+ T cells cooperate synergistically in hMPV eradication during primary infection, but CD4+ more than CD8+ T cells also enhanced clinical disease and lung pathology. Concurrent depletion of CD4+ and CD8+ T cells completely blocked airway obstruction as well as AHR. Despite impaired generation of neutralizing anti-hMPV antibodies in the absence of CD4+ T cells, mice had undetectable viral replication after hMPV challenge and were protected from clinical disease, suggesting that protection can be provided by an intact CD8+ T-cell compartment. Whether these findings have implications for naturally acquired human infections remains to be determined.

* Corresponding author. Mailing address: Department of Pediatrics, 301 University Blvd., Galveston, TX 77555-0366. Phone: (409) 747-0581. Fax: (409) 772-1761. E-mail: ancasola{at}utmb.edu

{triangledown} Published ahead of print on 18 June 2008.

{dagger} D.K. and E.L.B. contributed equally to this work.

Journal of Virology, September 2008, p. 8560-8569, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00699-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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