The Marmoset as an Animal Model of Influenza: Infection With A(H1N1)pdm09 and Highly Pathogenic A(H5N1) Viruses via the Conventional or Tracheal Spray Route

Abstract

To control infectious diseases in humans, it is important to understand the pathogenicity of the infecting organism(s). Although non-human primates, such as cynomolgus and rhesus macaques, have been used for influenza virus infection models, their size can limit their use in confined animal facilities. In this study, we investigated the susceptibility of marmosets to influenza viruses to assess the possibility of using these animals as a non-human primate model for influenza research. We first used an influenza A (H1N1)pdm09 virus to compare two inoculation routes: the conventional route, via a combination of the intratracheal, intranasal, ocular, and oral routes; and the tracheal spray route. In marmosets inoculated via the tracheal spray route, we found inflammation throughout the lungs and trachea. In contrast, in marmosets inoculated via the conventional route, the inflammation was confined to roughly the center of the lung. These data suggest that the tracheal spray route may be more suitable than the conventional route to inoculate marmosets with influenza viruses. We also tested an influenza A(H5N1) highly pathogenic avian influenza (HPAI) virus and found that some marmosets inoculated with this virus via the tracheal spray route showed weight loss, decreased body temperature, and loss of appetite and activity. The replication of this H5N1 virus in respiratory organs was confirmed. These results indicate the potential of marmosets as an animal model for infection with seasonal or HPAI viruses.

IFITM3 protects the heart during influenza virus infection

“…Although influenza virus primarily infects the lungs, cardiac complications of infection are also well documented (2)(3)(4)(5)(6)(7)(8). Influenza virus is known to be a cardiotropic virus that can disseminate from the lungs to infect heart tissue, particularly during severe infections (9)(10)(11)(12). Thus, the virus can cause myocarditis and cardiac dysfunction even in individuals without preexisting cardiovascular disease.…”

Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques

“…Non-human primates (NHP) form an important preclinical model in influenza virus research because of their close resemblance to humans with regard to anatomy, physiology, and cellular and humoral immune system, which are well characterized [ 8 , 9 , 10 ]. Studies in NHP infected with highly pathogenic avian H5N1 virus have contributed importantly to our knowledge on virus localization, pathology, and the stimulation of local and systemic innate and adaptive immune responses [ 11 , 12 , 13 , 14 , 15 , 16 ]. Similar to humans, NHP infected with H5N1 show an increase in proinflammatory cytokine and chemokine levels in the blood as well as in the lungs [ 11 , 13 , 15 ].…”

Discovery of a Novel Simian Pegivirus in Common Marmosets (Callithrix jacchus) with Lymphocytic Enterocolitis

“…The utility of common marmosets in research resulted in a recent increase in demand for these animals [ 6 ]. The Wisconsin National Primate Research Center (WNPRC) in Madison, Wisconsin, USA, houses a common marmoset colony typically consisting of about 240 common marmosets, which are used by researchers at the University of Wisconsin-Madison for groundbreaking research in neurological, neurobehavioral, and pharmacologic research, among many others [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”