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

Abstract

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 2¾10 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.

Animal models for influenza virus pathogenesis, transmission, and immunology

“…Signs such as ruffled fur, listlessness, and anorexia are either absent or so subtle as to not be readily apparent in guinea pigs. Increased nasal mucus can be appreciated in infected animals (Tang and Chong, 2009; Bouvier and Lowen, 2010), but in our experience this sign is not consistently obvious and would be difficult to follow clinically, although it can be appreciated histopathologically (Tang and Chong, 2009). …”

“…Similarly, ambient temperature and humidity fluctuates seasonally in temperate climates, even in buildings with environmental control systems, and transmission efficiency may depend on the time of year. Finally, different inoculating doses of virus are often used (Nishiura et al, 2013), which has been shown to impact transmissibility or pathogenicity in ferrets and in guinea pigs (Tang and Chong, 2009; Herfst et al, 2012). …”

Postmortem findings in eight cases of influenza A/H1N1

“…Studies performed in guinea pigs showed that a neutrophilic infiltrate can be present in the very early stages of H1N1 infection causing acute bronchiolitis, bronchointerstitial pneumonia, and alveolitis. 13 However, other studies found that an outstanding feature in the early stage of infection is the absence of neutrophils in the infiltrate. 12 Even though it may be convenient to correlate the clinical findings with the histopathological findings, it remains unclear how the histopathological findings in H1N1 infection truly correlate with clinical comorbidities and bacterial coinfection because tissue sampling, patient susceptibilities, disease onset, and grading and interpretation of the histopathological findings are variable.…”

Novel H7N9 Influenza Virus Shows Low Infectious Dose, High Growth Rate, and Efficient Contact Transmission in the Guinea Pig Model

“…A key advantage of the model, compared to mice, is that guinea pigs are highly susceptible to infection with human strains (requiring no prior adaptation) (19)(20)(21). In addition, human influenza viruses show tissue tropism and kinetics of viral growth similar to those seen in uncomplicated influenza in humans (19,22,23). Importantly, human influenza virus strains transmit among guinea pigs by contact and respiratory droplet routes, whereas swine-adapted and some highly pathogenic avian influenza viruses transmit poorly and lowpathogenicity avian strains do not transmit (19)(20)(21)(24)(25)(26)(27)(28)(29)(30)(31).…”

“…A disadvantage is that, to date, overt signs of disease have not been detected in influenza virus-infected guinea pigs. Nevertheless, rhinitis and bronchointerstitial pneumonia have been described (22,32). The utility of the guinea pig model is underlined by the fact that, since 2006, many additional labs have adopted it for the study of influenza virus transmission (33)(34)(35)(36)(37)(38).…”