Multiple Organ Invasion by Viruses: Pathological Characteristics in Three Fatal Cases of the 2009 Pandemic Influenza A/H1N1

Ru, Yongxin; Li, Yuechuan; Zhao, Yongkun; Zhao, Shi-Xuan; Yang, Jingping; Zhang, Huamei; Pang, Tianxiang

doi:10.3109/01913123.2011.574249

Cited by 15 publications

(11 citation statements)

References 20 publications

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“…Efficient dissemination of F virus might have contributed also to increase the severity of the infection. Accordingly, viral particles have been found in the hearts of both domestic ducks infected with H5N1 highly pathogenic avian virus [55] and fatal cases of 2009 pandemic infected patients [56]. Extrapulmonary complications of influenza virus infection have been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

et al. 2013

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Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32).

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Section: Discussionmentioning

confidence: 99%

Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

et al. 2013

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“…Among them, the direct infection and lysis of muscle cells [1,49] is supported by the isolation of influenza viruses from IAM patients’ skeletal muscle samples, or the observation of viral particles in muscle tissue [30-33,35,39,40]. Extra-pulmonary replication of influenza viruses is rarely reported in infected individuals, but viremia is sometimes detected even in patients with mild disease and was found in pandemic influenza A (H1N1) patients with acute illness and with elevated CK levels [49].…”

Section: Discussionmentioning

confidence: 99%

“…In one case, viral particles and viral antigens in muscle cells were also detected in situ [30]. More recently, three fatal cases of pneumonia due to the new influenza A H1N1 pandemic virus showed multiple organ invasion with viral particles being detected in the skeletal muscle [40]. …”

Section: Introductionmentioning

confidence: 99%

Productive Infection of Human Skeletal Muscle Cells by Pandemic and Seasonal Influenza A(H1N1) Viruses

et al. 2013

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Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1) in 2009. The pathogenesis of these influenza-associated myopathies (IAM) remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1) isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes) were highly susceptible to infection by both influenza A(H1N1) isolates, whereas undifferentiated cells (i. e. myoblasts) were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP) expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients.

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“…198,199 Post-mortem study of three fatal cases of A(H1N1)pdm09 virus infection demonstrated viral particles in the endothelial cells, sinusoidal epithelial cells, and hepatic macrophages. 200 Influenza virus has also been isolated and cultured from the liver of a patient that died of influenza A infection. 201 immediately following infection and demonstrated a delayed response to corticosteroids.…”

Section: Hepatic Complications Of Influenzamentioning

confidence: 99%

The hidden burden of influenza: A review of the extra‐pulmonary complications of influenza infection

Sellers

Hagan

Hayden

et al. 2017

Influenza Resp Viruses

325

308

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Severe influenza infection represents a leading cause of global morbidity and mortality. Although influenza is primarily considered a viral infection that results in pathology limited to the respiratory system, clinical reports suggest that influenza infection is frequently associated with a number of clinical syndromes that involve organ systems outside the respiratory tract. A comprehensive MEDLINE literature review of articles pertaining to extra‐pulmonary complications of influenza infection, using organ‐specific search terms, yielded 218 articles including case reports, epidemiologic investigations, and autopsy studies that were reviewed to determine the clinical involvement of other organs. The most frequently described clinical entities were viral myocarditis and viral encephalitis. Recognition of these extra‐pulmonary complications is critical to determining the true burden of influenza infection and initiating organ‐specific supportive care.

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Multiple Organ Invasion by Viruses: Pathological Characteristics in Three Fatal Cases of the 2009 Pandemic Influenza A/H1N1

Cited by 15 publications

References 20 publications

Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

Productive Infection of Human Skeletal Muscle Cells by Pandemic and Seasonal Influenza A(H1N1) Viruses

The hidden burden of influenza: A review of the extra‐pulmonary complications of influenza infection

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