Influenza A virus infection induces liver injury in mice

Abstract

A B S T R A C TRespiratory infections such as SARS-CoV in humans are often accompanied by mild and self-limiting hepatitis. As a respiratory disease, influenza A virus (IAV) infection can lead to hepatitis, but the mechanism remains unclear. This study aimed to investigate the occurrence of hepatitis by establishing a model for infected mice for three different subtypes of respiratory IAVs (H1N1, H5N1, and H7N2). Histological analysis was performed, and results showed increase serum aminotransferase (ALT and AST) levels and evident liver injury on days 3 and 7, especially on day 5 post infection. Immunohistochemistry (IHC) results indicated a wide distribution of IAV's positive signals in the liver of infected mice. Real-time PCR results further revealed a similar viral titer to IHC that presented a remarkedly positive correlation with histology injury. All these data showed that the mouse model suitably contributed valuable information about the mechanism underlying the occurrence of hepatitis induced by respiratory influenza virus.

Impact of COVID-19 on liver function: results from an internal medicine unit in Northern Italy

“…First, we did not provide a causal effect between COVID-19 and abnormal liver function tests, as liver specimens were not obtained from these patients. Hence, a direct cytopathic effect caused by the virus could not be ascertained, even if, according to animal models and small case series, other respiratory tract viruses were shown to have a direct cytopathic effect in the liver [28,29]. Given the retrospective, real-life nature of the study, we could not establish whether other confounding factors played a role (e.g., previous intake of medications, other undiagnosed liver diseases).…”

Prognostic Significance of End-Stage Liver Diseases, Respiratory Tract Infection, and Chronic Kidney Diseases in Symptomatic Acute Hepatitis E

“…It is interesting that respiratory tract infection is a risk factor of acute HEV patients, and this may be due to the fact that patients with acute HEV infection, especially the severe cases usually have poor immunity, which also makes them more susceptible to respiratory pathogens, further aggravates the symptoms caused by HEV virus. Furthermore, studies have shown that respiratory infection increases serum aminotransferase (ALT and AST) levels and causes liver histopathologic injury ( Zhang et al., 2019 ). Respiratory infections elicit robust hepatic transcriptome remodeling within hours of experimentally induced pneumonia ( Quinton et al., 2009 ).…”

Detection of Virus-Related Sequences Associated With Potential Etiologies of Hepatitis in Liver Tissue Samples From Rats, Mice, Shrews, and Bats

“…None of the serum samples was positive in the detection of sequences related to influenza A virus by using PCR, which indicated that viruses related to influenza A virus in these animals may be hepatotropic. Previous studies showed that the influenza A virus can cause liver injury in human and laboratory rats ( Morocco et al, 2014 ; Nonaka et al, 2019 ; Zhang et al, 2019 ). These indicated that like the human influenza A virus, the viruses related to the influenza A virus in animals might also be a causative agent of hepatitis.…”

“…Human liver diseases related to infection by the influenza A virus has been documented. In addition, a previous study showed that infection with the influenza A virus can cause hepatitis in an animal model ( Morocco et al, 2014 ; Nonaka et al, 2019 ; Zhang et al, 2019 ). Some viruses, like pegivirus ( Mrzljak and Tabain, 2019 ), TTV ( Paraná and Lyra, 2000 ), KIs-V ( Lole et al, 2017 ), and SEN-V ( Sehgal, 2003 ), are considered to be the potential causes of hepatitis.…”