Monday Article #67: Influenza A: Get the fact not the flu
The cause of influenza is Influenza A virus (IAV), which raises concerns for world health. The Orthomyxoviridae RNA virus family includes influenza viruses (Kalarikka and Jaishankar, 2019). IAV causes sporadic pandemics, which result in increased human and financial damage, as well as seasonal infections, which cause 3-5 million cases of severe sickness annually. It is crucial to comprehend the early stages of IAV infection since they provide the best opportunity for intervention (Sempere Borau and Stertz, 2021). The influenza virus causes the flu. However, it can also have severe symptoms such as head and body aches, fever, sore throat as well as respiratory problems. Winter is when influenza is most prevalent as an epidemic of illness can occur (Cleveland Clinic, 2022) .Hemagglutinin (H) and neuraminidase (N), two proteins found on the surface of influenza A viruses, are used to categorise them into different subtypes (Centers for Disease Control and Prevention, n.d.). H1 through H18 and N1 through N11, respectively, are the distinct hemagglutinin subtypes and neuraminidase subtypes. Although more than 130 different influenza A subtype combinations have been found in nature, mostly in wild birds, there may be many more given the tendency for virus "reassortment." Influenza viruses exchange gene segments through a process called reassortment (Centers for Disease Control and Prevention, n.d.).
Figure 1: The structure of the Influenza A virus
Figure 2: The replicative cycle of the Influenza virus
In the nose, throat and lungs of mammals and the intestines of birds, influenza viruses attach via hemagglutinin to sialic acid sugars on the surfaces of epithelial cells. The cell imports the virus by endocytosis after the hemagglutinin is broken down by a protease. The convergence of virions to the microtubule organising centre, their interactions with acidic endosomes, and their entry into the target endosomes for genome release are all known to occur. Two things happen as a result of the endosome's acidic environment once it enters the cell. First, the viral envelope and the vacuolar membrane are joined together by the hemagglutinin protein. Next, protons can pass through the viral envelope and acidify the virus's core through the M2 ion channel. This causes the virus's core to disassemble and release the viral RNA and core proteins. Following this, the RNA-dependent RNA polymerase, auxiliary proteins and viral RNA (vRNA) molecules are released into the cytoplasm. The core protein and the vRNA form a complex which is transported into the cell nucleus, where the corresponding positive-sense vRNA is started to be transcribed by the RNA-dependent RNA polymerase .
The vRNA either stays in the nucleus or moves into the cytoplasm and is translated. Newly produced viral proteins are either taken back into the nucleus to bind vRNA and generate new viral genome particles or released through the Golgi apparatus onto the cell surface.
In addition to blocking the translation of host-cell mRNAs, other viral proteins also degrade cellular mRNA and use the nucleotides liberated for vRNA synthesis in the host cell.
A virion is made up of viral proteins, RNA-dependent RNA polymerase and negative-sense vRNAs that will eventually become the genome of new viruses. Molecular clusters of hemagglutinin and neuraminidase form a cell membrane bulge. This membrane protrusion is where the viral RNA and core proteins enter after leaving the nucleus. In a sphere of the host phospholipid membrane, the mature virus buds out from the cell and picks up hemagglutinin and neuraminidase with this membrane coat. As before, the viruses attach to the cell via hemagglutinin; once the mature viruses' neuraminidase has cleaved sialic acid remnants from the host cell, they separate. As a result, drugs that suppress neuraminidase, such oseltamivir, stop viral reproduction and the spread of new infectious viruses. The host cell dies following the emergence of fresh influenza viruses.
Influenza transmission in enclosed spaces can be reduced with the help of public health initiatives (Nguyen and Derlet, n.d.). The spread of influenza is slowed down by increased surveillance, including daily temperature taking, rapid reporting, isolation during home medical leave as well as segregation of smaller subgroups. In one study, the application of these strategies reduced the proportion of symptomatic illness attributable to influenza from 12% to roughly 4% (Nguyen and Derlet, n.d.). Resting in bed is usually beneficial for influenza patients. The majority of influenza patients recover in 3 days, but the illness may linger for weeks (Nguyen and Derlet, n.d.).
Patients most frequently need to be admitted to the hospital when the flu aggravates underlying chronic conditions. Some patients, particularly the elderly, may be too frail to care for themselves at home on their own. The direct pathologic effects of influenza can occasionally make hospitalisation necessary, mostly due to the pneumonia (Nguyen and Derlet, n.d.)
The influenza vaccination induces the production of antibodies that are specific to the illness, providing protection against the influenza virus (Kalarikka and Jaishankar, 2019). When antibodies against neuraminidase (N) are present, they can effectively aggregate the viruses on the cell surface and less viruses are discharged from infected cells. Regarding the induction of immunity, the influenza virus's hemagglutinin protein has two structural components, a head and a stalk. Antibodies that give protective immunity against influenza viruses mostly target the head (Kalarikka and Jaishankar, 2019).
While humoral immunity predominates, cell-mediated immunity also plays a crucial part in immunisation to influenza, making the immune defence mechanism more intricate. An immune response against the flu takes two weeks to develop after immunisation (Kalarikka and Jaishankar, 2019). The effectiveness of a vaccine is influenced by a variety of host characteristics, including age, general health, genetics and antigenic matching between the vaccine and viruses that are in circulation (Kalarikka and Jaishankar, 2019).
Biology LibreTexts. (2017). Replicative Cycle of Influenza A. Retrieved from https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/09%3A_Viruses/9.09%3A_Negative-Strand_RNA_Viruses_in_Animals/9.9C%3A_Replicative_Cycle_of_Influenza_A.
Centers for Disease Control and Prevention. (n.d.). Types of Influenza Viruses. Retrieved from https://www.cdc.gov/flu/about/viruses/types.htm.
Cleveland Clinic. (2022). Influenza (Flu): Treatment, Prevention, Symptoms vs Cold. Retrieved from https://my.clevelandclinic.org/health/diseases/4335-influenza-flu.
Kalarikkal, S.M. and Jaishankar, G.B. (2019). Influenza Vaccine. StatPearls Publishing. [Online] Available at: https://www.ncbi.nlm.nih.gov/books/NBK537197/. (Accessed: 6 August 2023)
Nguyen, H.H and Derlet, R.W. (n.d.). Influenza Treatment & Management. Retrieved from https://emedicine.medscape.com/article/219557-treatment?form=fpf
Sempere Borau, M. and Stertz, S. (2021). ‘Entry of influenza A virus into host cells — recent progress and remaining challenges;, Current Opinion in Virology, 48, pp.23–29. DOI: https://doi.org/10.1016/j.coviro.2021.03.001. (Accessed: 6 August 2023)
This article was prepared by Thiiben A/L Krishnan Sami