Table 4.

Key Animal Models of Muscular Disease with Respiratory Influenza Virus Infection

Disease Model	Animal Model	Influenza Strain (and treatment)	Observed Effects	Proposed Effectors or Mechanisms	Ref
Respiratory influenza infection	C57BL/6J mice Atrogin-1−/− mice	H1N1 A/WSN/1933	Decreased muscle weight Decreased forelimb strength	Increased muscular atrogin-1 expression Increased sera IL-6 levels IL-6 induces FoxO3a increasing atrogin-1 expression	[136]
Aging	C57BL/6J mice Young: 2.5–4 months Aged: 19–22 months	H1N1 A/Puerto Rico/8/34	Decreased mobility, more pronounced in aged mice Altered gait kinetics, more pronounced in aged mice	IL6 expression in skeletal muscle of mice at all ages TNF and CXCL10 expression in skeletal muscle of aged mice Increased expression of muscle degradation genes (FOXO1, ATROGIN1, MuRF1) Decreased expression of muscle growth genes (IGF1, PAX7, MYOD1, MYOG)	[137]
	C57BL/6J mice Young: 9–11 weeks Aged: 18 months	H1N1 A/WSN/1933	Decreased muscle weight and cross-sectional areas Aged mice fail to recover muscle function Muscle regeneration is impaired in aged mice	Increased sera IL-6 levels Increased muscular atrogin-1 expression Tissue-resident CX3CR1+ skeletal muscle macrophages expand in young mice to induce regeneration Skeletal muscle macrophages in aged mice have persistent MHCII expression	[138]
	C57BL/6J mice Young: 2.5–4 months Aged: 19–22 months	PR8 NP vaccination followed by H1N1 A/Puerto Rico/8/34	Vaccination prevented reductions in voluntary activity Vaccination prevented reductions in grip strength Vaccination prevented losses in IIB fiber cross-sectional areas	Vaccination prevented persistent sera cytokine expression (IL-6, CXCL10) in aged mice Vaccination prevents muscular MuRF-1 expression	[140]