Myositis induced by influenza A in mice.

Abstract

As an approach to the mechanism of myalgia and myositis observed frequently in human influenza, virological and morphological studies were carried out on experimental influenza in mice. Influenza virus A/PR8/34 (HoNi) was inoculated by the intranasal or intramuscular route. Muscle was examined histologically, by electron microscopic and immunofluorescent techniques. Virus isolation was also carried out from muscle, lung, spleen and blood. Myositis was induced predominantly when virus was inoculated into the hamstring muscles of young mice (three-week-old, DDy strain). In mice inoculated intranasally, myositis was not observed. Significant changes in muscle were observed neither in congenitally athymic nude mice inoculated with active virus nor in DDy mice inoculated with inactivated virus. On the other hand, the degree of myositis in adult mice (seven-week-old) was milder than that in younger mice. Myositis developed from the epimydium surrouding muscle cells, and healed approximately 14th days after inoculation. In spite of obviousmyositis, no evidence for multiplication of virus in muscle was obtained by virus isolation and immunofluorescent studies. The virus was stained by fluorescent antibody method mainly in fibroblasts and adipose tissues near muscle cells. A similar outcome was seen in the muscle of nude mice. Thus, host factors such as age, species and immune system might play a role in the susceptibility of muscle to influenza virus. The results obtained from these studies suggest that viral toxicity and T cell function, rather than the virus itself, may induce inf luenzal myositis.

Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy

“…Supporting this, Nevalainen et al [ 53 ] showed that mature muscle fibers do not produce viral progeny, though a non-permissive infection occurs. Indeed, in vivo studies have shown that a non-permissive infection may occur in the skeletal muscle [ 25 ], though this seems more likely when intramuscular flu infection models are used [ 24 , 26 ]. Since we performed intranasal infections, similar to the natural route of infection in humans, it is unlikely this would occur; however, it is still possible that this non-permissive infection leads to viral copies below our detectible limit and direct viral infection, or perhaps the presence of viral particles, may contribute to muscle degradation.…”

“…While some in vitro studies have shown that myoblasts and myotubes may be susceptible to infection and might produce live viral progeny [ 18 - 20 ], isolation of virus from muscle biopsies is rare [ 12 , 21 - 23 ]. In vivo murine experiments showed that a non-permissive infection is possible in mature muscle fibers, though this is more likely with intramuscular inoculation [ 24 - 26 ], so the clinical relevance of these experiments remains entirely unclear.…”

Influenza-Associated Myositis in Children

“…Additionally, Gamboa et al [38] demonstrated myxovirus-like particles by muscle electron microscopy. Experimental studies [40][41][42] established that influenza virus is capable of infecting both animal and human muscle cells, with immature muscle cells being more permissive to infection than mature cells. This finding may explain the occurrence of IAM predominantly in children.…”

Clinical Characteristics of 118 Pediatric Patients With Acute Benign Myositis Associated With Influenza A Virus Infection

“…The mechanism of this process is unclear, and the most proposed causes of virus-induced muscle damage are direct invasion of the muscle by viral particles and virus-triggered immune-mediated muscle damage. 2,4,20,24,25 Our study suggested that the course of early fever and sudden lower limb pain after defervescence may be related to immune-mediated muscle damage caused by the virus. When fever occurred simultaneously with myalgia, this may have been related to the direct invasion of the muscle by viral particles.…”

“…The influenza virus is more likely to infect immature cells. [20][21][22][23] This difference may be related to the higher incidence of benign myositis in preschool-and school-age children. The reason for the male predominance is not clear but may be related to males having greater physical activity, a genetic predisposition in males, or unknown metabolic defects in males.…”