Histopathology and growth kinetics of influenza viruses (H1N1 and H3N2) in the upper and lower airways of guinea pigs.

Recent investigations have shown that guinea pigs are important for the study of influenza A virus (IAV) transmission. However, very little is known about IAV replication and histopathology in the guinea pig respiratory tract. Here, we describe viral growth kinetics, target cells and histopathology in the nasosinus, trachea and lungs of IAV-infected guinea pigs. We found that guinea pigs infected with either A/Puerto Rico/8/34 (H1N1) or A/Hong Kong/8/68 (H3N2) developed a predominantly upper airway infection with high nasal viral titres. IAV grew to moderate titres in the lungs but induced marked inflammatory responses, resulting in severe bronchopneumonia and alveolitis. Although non-lethal at the high dose of 2x10(6) p.f.u., infections with these IAV strains were associated with reduced weight gain. IAV infection in guinea pigs is characterized by extensive viral replication in the ciliated nasal epithelial cells followed by heavy nasal mucus secretion.

Enhanced expression of murine beta-defensins (MBD-1, -2,- 3, and -4) in upper and lower airway mucosa of influenza virus infected mice.

Although defensins are known to inhibit the replication of human influenza A virus (IAV) in vitro, their in vivo expression during IAV infection is not known. Here we investigated mRNA and protein expression of several beta-defensins in the airways of IAV infected mice. Expression of murine beta-defensin (MBD)-3 and -4 was enhanced (3 to 5-fold, p<0.01) in infected lungs, trachea and sinonasal mucosa. MBD-3 and -4 expressions were correlated with the time course of acute IAV infection suggesting their induction by IAV infection. Infected mice also showed increased levels of surfactant protein-D especially in the sinonasal mucosa. MBD-3 and -4 were localized to the conducting airway epithelial cells but not the alveolar tissue. We conclude that IAV infection upregulated the expression of inducible beta-defensins in both the upper and lower airways. These novel findings suggest that beta-defensins might contribute to innate and adaptive immune responses targeted against IAV infection.

High level expression of human epithelial beta-defensins (hBD-1, 2 and 3) in papillomavirus induced lesions.

BACKGROUND: Epithelial defensins including human beta-defensins (hBDs) and alpha-defensins (HDs) are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. RESULTS: Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP) and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR) assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p < 0.01) suggesting that they were co-inducible in papillomavirus induced lesions. Unlike hBDs, only low levels of HD5 and HD6 were detectable in papillomas and in oral mucosa. CONCLUSION: Human beta-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.