The Contribution of Viral Proteins to the Synergy of Influenza and Bacterial Co-Infection

Abstract

A severe course of acute respiratory disease caused by influenza A virus (IAV) infection is often linked with subsequent bacterial superinfection, which is difficult to cure. Thus, synergistic influenza–bacterial co-infection represents a serious medical problem. The pathogenic changes in the infected host are accelerated as a consequence of IAV infection, reflecting its impact on the host immune response. IAV infection triggers a complex process linked with the blocking of innate and adaptive immune mechanisms required for effective antiviral defense. Such disbalance of the immune system allows for easier initiation of bacterial superinfection. Therefore, many new studies have emerged that aim to explain why viral–bacterial co-infection can lead to severe respiratory disease with possible fatal outcomes. In this review, we discuss the key role of several IAV proteins—namely, PB1-F2, hemagglutinin (HA), neuraminidase (NA), and NS1—known to play a role in modulating the immune defense of the host, which consequently escalates the development of secondary bacterial infection, most often caused by Streptococcus pneumoniae. Understanding the mechanisms leading to pathological disorders caused by bacterial superinfection after the previous viral infection is important for the development of more effective means of prevention; for example, by vaccination or through therapy using antiviral drugs targeted at critical viral proteins.

The clinical predictors of and vaccine protection against severe influenza infection in children

“…Influenza A proteins may play a role in the progression of bacterial superinfection, in which neuraminidase promotes entry to receptors and nutrients for S. pneumoniae; other proteins, such as nonstructural protein 1 (NS1) and PB1-F2, disrupt the regulation of the interferon response and inflammatory process. 20 In our study, the most common coinfecting bacterial respiratory pathogens were Staphylococcus aureus, followed by S. pneumoniae and Haemophilus influenzae. A meta-analysis and systemic review pointed out that the predominant coinfecting organism in the studies was S. pneumoniae, followed by S. aureus, but many other organisms were also found to cause infections.…”

“…Influenza virus paves the way for subsequent bacterial infection by disrupting the anatomic barrier or mucosal surface in the respiratory system. Influenza A proteins may play a role in the progression of bacterial superinfection, in which neuraminidase promotes entry to receptors and nutrients for S. pneumoniae ; other proteins, such as nonstructural protein 1 (NS1) and PB1‐F2, disrupt the regulation of the interferon response and inflammatory process 20 . In our study, the most common coinfecting bacterial respiratory pathogens were Staphylococcus aureus , followed by S. pneumoniae and Haemophilus influenzae .…”

Cooperation and cheating orchestrateVibrioassemblages and polymicrobial synergy in oysters infected with OsHV-1 virus

“…A virus and Streptococcus pneumonia [4,5] or Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis [6][7][8]. Synergy has also been reported between viruses such as Herpes virus simplex and HIV [9,10].…”

The induction of virus-neutralizing antibodies in influenza A-infected mice treated with Oseltamivir phosphate: effect of dosage and scheduling

“…The severity of the disease is influenced by many factors, including the virulence of the virus strain, which caused the infection, but especially by the status of the host immune system. These factors determine whether the common secondary bacterial infection, in praxis often suppressed by the application of antibiotics, will be associated with the primary viral infection (Mikušová et al, 2022). However, antibiotics may not help to cure the bacterial co-infection if the infected individuals are immuno-compromised or suffer from other chronic diseases (McCullers, 2004(McCullers, , 2011.…”

“…However, antibiotics may not help to cure the bacterial co-infection if the infected individuals are immuno-compromised or suffer from other chronic diseases (McCullers, 2004(McCullers, , 2011. It was shown that a synergism occurs during influenza and bacteria coinfection (Kash and Taubenberger, 2015;Karlson et al, 2017;Mikušová et al, 2022). Because the influenza infection causes the damage of the respiratory epithelium, the accessibility of epithelial cell surfaces for bacterial infection is increased and, subsequently, u n c o r r e c t e d…”