ENHANCED SURFACTANT PROTEIN AND DEFENSIN MRNA LEVELS AND REDUCED VIRAL REPLICATION DURING PARAINFLUENZA VIRUS TYPE 3 PNEUMONIA IN NEONATAL LAMBS

Authors: GRUBOR, BRANKA - IOWA STATE UNIVERSITY; GALLUP, JACK - IOWA STATE UNIVERSITY; MEYERHOLZ, DAVID - IOWA STATE UNIVERSITY; CROUCH, ERIKA - UNIVERSITY OF WASHINGTON; EVANS, RICHARD - IOWA STATE UNIVERSITY; BROGDEN, KIM; LEHMKUHL, HOWARD; ACKERMANN, MARK - IOWA STATE UNIVERSITY

Submitted to: Clinical and Diagnostic Laboratory Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/2/2004
Publication Date: 5/2/2004
Citation: Grubor, B., Gallup, J.M., Meyerholz, D.K., Crouch, E.C., Evans, R.B., Brogden, K.A., Lehmkuhl, H.D., Ackermann, M.R. 2004. Enhanced surfactant protein and defensin mrna levels and reduced viral replication during parainfluenza virus type 3 pneumonia in neonatal lambs. Clinical and Diagnostic Laboratory Immunology. 11(3):599-607.

Interpretive Summary: Paramyxovirus infections are a major cause of respiratory disease in ruminants. Immunity to paramyxovirus infections are often not long lasting or protective. In contrast, innate immune factors, such as defensins and surfactant proteins, are increasingly recognized for their activities against viral infections. The extent to which parainfluenza type 3 virus infection in neonatal lambs altered the production of defensins and surfactant proteins was determined. Increased defensins and surfactant proteins were detected at all times postinoculation and this increased expression occurs concurrently with decreased viral replication. The results of this study provides information useful to the development of clinical treatment of paramyxovirus infections.

Technical Abstract: Defensins and surfactant protein A (SP-A) and SP-D are antimicrobial components of the pulmonary innate immune system. The purpose of this study was to determine the extent to which parainfluenza type 3 virus infection in neonatal lambs alters expression of sheep beta-defensin 1(SBD-1), SP-A, and SP-D, all of which are constitutively transcribed by respiratory epithelia. Parainfluenza type 3 viral antigen was detected by immunohistochemistry (IHC) in the bronchioles of all infected lambs 3 days postinoculation and at diminished levels 6 days postinoculation, but it was absent 17 days postinoculation. At all times postinoculation, lung homogenates from parainfluenza type 3 virus-inoculated animals had increased SBD-1, SP-A, and SP-D mRNA levels as detected by fluorogenic real-time reverse transcriptase PCR. Protein levels of SP-A in lung homogenates detected by quantitative-competitive enzyme-linked immunosorbent assay and protein antigen of SP-A detected by IHC were not altered. These studies demonstrate that parainfluenza type 3 virus infection results in enhanced expression of constitutively transcribed innate immune factors expressed by respiratory epithelia and that this increased expression occurs concurrently with decreased viral replication.