Herpes Simplex Virus Type 1 Infection Facilitates Invasion of Staphylococcus aureus into the Nasal Mucosa and Nasal Polyp Tissue

Abstract

Background Staphylococcus aureus ( S. aureus ) plays an important role in the pathogenesis of severe chronic airway disease, such as nasal polyps. However the mechanisms underlying the initiation of damage and/or invasion of the nasal mucosa by S. aureus are not clearly understood. The aim of this study was to investigate the interaction between S. aureus and herpes simplex virus type 1 (HSV1) in the invasion of the nasal mucosa and nasal polyp tissue. Methodology/Principal Findings Inferior turbinate and nasal polyp samples were cultured and infected with either HSV1 alone, S. aureus alone or a combination of both. Both in turbinate mucosa and nasal polyp tissue, HSV1, with or without S. aureus incubation, led to focal infection of outer epithelial cells within 48 h, and loss or damage of the epithelium and invasion of HSV1 into the lamina propria within 72 h. After pre-infection with HSV1 for 24 h or 48 h, S. aureus was able to pass the basement membrane and invade the mucosa. Epithelial damage scores were significantly higher for HSV1 and S. aureus co-infected explants compared with control explants or S. aureus only-infected explants, and significantly correlated with HSV1-invasion scores. The epithelial damage scores of nasal polyp tissues were significantly higher than those of inferior turbinate tissues upon HSV1 infection. Consequently, invasion scores of HSV1 of nasal polyp tissues were significantly higher than those of inferior turbinate mucosa in the HSV1 and co-infection groups, and invasion scores of S. aureus of nasal polyp tissues were significantly higher than those of inferior turbinate tissues in the co-infection group. Conclusions/Significance HSV1 may lead to a significant damage of the nasal epithelium and consequently may facilitate invasion of S. aureus into the nasal mucosa. Nasal polyp tissue is more susceptible to the invasion of HSV1 and epithelial damage by HSV1 compared with inferior turbinate mucosa.

A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS)

“…Another possible contributing factor to invasion of S. aureus could be pre-infection with herpes simplex virus type 1 (HSV1). Wang et al showed evidence suggestive of a significant damage to the nasal epithelium by HSV1 infection that could consequently facilitate invasion of S. aureus into the nasal mucosa [71]. …”

Decreased expression of type I (IFN-β) and type III (IFN-λ) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps

“…[2][3][4] It has been suggested that viral respiratory tract infection (VRI) influences the development or progressive course of CRS through various means. 5,6 In vitro studies demonstrated that VRIs can damage the epithelial cells covering the sinonasal cavity, resulting in dysfunction of the epithelial barrier and increased bacterial adhesion. 5,6 The interferon response of airway epithelial cells is critical for defense against viral infection because it is required to suppress viral replication.…”

Viruses and bacteria in Th2‐biased allergic airway disease

“…Conversely, the exposure of H. influenzae to primary human epithelial cells significantly enhanced the binding of HRV16, probably through the up-regulation of intercellular adhesion molecule and toll-like receptor-3 expression (89). Our recent study also showed that herpes simplex virus type 1 infection facilitates the invasion of S. aureus into the nasal mucosa and CRSwNP tissue (90). In humans with acute respiratory illnesses, however, children with HRSV and Mycoplasma pneumonia co-infection had more severe airway inflammation than those with HRSV infection alone (91); bacteria (influenzae, catarrhalis, and pneumoniae) are more likely to be detected among virusnegative specimens compared to virus-positive burden (92).…”