Understanding the Molecular Interactions Between Influenza A Virus and Streptococcus Proteins in Co-Infection: A Scoping Review

Abstract

Influenza A virus infections are known to predispose infected individuals to bacterial infections of the respiratory tract that result in co-infection with severe disease outcomes. Co-infections involving influenza A viruses and streptococcus bacteria result in protein-protein interactions that can alter disease outcomes, promoting bacterial colonisation, immune evasion, and tissue damage. Focusing on the synergistic effects of proteins from different pathogens during co-infection, this scoping review evaluated evidence for protein-protein interactions between influenza A virus proteins and streptococcus bacterial proteins. Of the 2366 studies initially identified, only 32 satisfied all the inclusion criteria. Analysis of the 32 studies showed that viral and bacterial neuraminidases (including NanA, NanB and NanC) are key players in desialylating host cell receptors, promoting bacterial adherence and colonisation of the respiratory tract. Virus hemagglutinin modulates bacterial virulence factors, hence aiding bacterial internalisation. Pneumococcal surface proteins (PspA and PspK), bacterial M protein, and pneumolysin (PLY) enhance immune evasion during influenza co-infections thus altering disease severity. This review highlights the importance of understanding the interaction of viral and bacterial proteins during influenza virus infection, which could provide opportunities to mitigate the severity of secondary bacterial infections through synergistic mechanisms.

Keywords: Streptococcus spp.; bacterial colonisation; co-infection; influenza A virus; molecular interactions; neuraminidase; therapeutics; viral–bacterial synergy.

Figure 1

Illustration of primary IAV infection and secondary Streptococcus infection. The ciliated epithelial cells and underlying mucosal layers are damaged due to the sialidase activity of the viral NA. Viral infections impair the immune response, induce apoptosis, and cause inflammation, leading to tissue damage. This will enhance susceptibility to secondary bacterial infection 3–7 days post-viral infection. Created with BioRender.com.

Figure 2

Flowchart summarising the process of the literature identification, screening, and selection for the scoping review.

Figure 3

Direct interactions between Influenza A virus (IAV) and Streptococcus during co-infection. (A) Streptococcus adhesion to host epithelial cells, facilitated by viral factors during co-infection. (B) Co-infection of Influenza A virus (IAV) and Streptococcus, where viral particles enhance bacterial colonisation on host tissues. (C) Receptor binding between viral proteins and bacterial surface components, promoting bacterial adherence to host cells. (D) Virion stability is affected by bacterial interaction, which may facilitate the persistence of viral particles on host cells and enhance co-infection severity (Created with BioRender.com).