Influenza A virus is a member of the Orthomyxoviridae family that is made up of 8 negative-sense single-stranded RNA segments that codes for 11 viral genes. The high mutation rates associated with the genome makes influenza incredibly difficult to prevent annual epidemics, resulting in millions of hospitalisation and thousands of deaths. Acute and early diagnosis of influenza A viral infections are important for rapid initiation of antiviral therapy to minimise viral related mortality and morbidity during both seasonal epidemics and pandemics. Currently, FDA approved rapid molecular assays are the commonly used method for the diagnosis of influenza in hospitalised patients.
Many antiviral drugs including zanamivir (Relenza), oseltamivir (Tamiflu), rimantadine and amantadine are available for the treatment, but the use of drugs results in the development of drug resistance and adverse side effects on the central nervous system. Resistance to antiviral drugs is an increasing concern in the affected population, where exponential viral replication and prolonged drug exposure leads to the formation of resistant influenza strains. Even though antiviral medications have proved to control viral replication, vaccination remains the most cost-effective and practical method to control and prevent serious complications resulting from influenza A.
Epidemiology
Influenza, known as flu, is a respiratory infection caused by influenza A virus type in human and among the most important because they are known to cause high morbidity and mortality (Vemula et al., 2016). Influenza viruses belong to the Orthomyxoviridae family, which consists of four influenza genera: influenza virus A, B, C and D. Each of the virus type of classified based on the differences found in their nucleoprotein (NP) and the matrix (M).
It has been reported that each year, influenza A type causes seasonal widespread epidemics and pandemics, accounting for 4- 5 million cases with severe illness, 400,000-500,000 deaths and more than 200,000 hospitalisations worldwide (10-15% of the population) (Meštrović, 2018). Influenza widespread has occurred since ancient times and is associated with high mortality rates in elderly, infants and people diagnosed with chronic diseases (Hirsch, 1883).
Seasonal influenza epidemics can occur frequently in both Southern and Northern hemispheres. Seasonal epidemics occur mainly during winter, compared to a tropical region, in which it may appear throughout the year, leading to more irregular outbreaks. Not much is known about epidemics of Influenza in tropical regions but assumed that it occurs throughout the year. Influenza epidemics are distinguished from each other by the severity of the infection. In 1918, the Spanish flu caused 35-40 million deaths while Asian influenza outbreak in 1957 and Hong Kong influenza in 1968 resulted in 1.5 – 2 million and 1 million deaths (Fauci, 2006).
Influenza A structure and function
In general, all the virus types are made up of two essential components: i] a nucleic acid genome, ii] a genome protecting protein capsid. Both the essential components together known as the nucleocapsid. Unlike other virus types, influenza A is made up of an additional lipid bilayer, derived from the host cell in which the virus attaches and multiplies. The spikes found in the lipid bilayer are glycoproteins that consist of proteins attached to sugars known as hemagglutinin (HA) and neuraminidase (NA) (see figure 1).
HA is the most abundant (80%) envelope protein then followed by NA (17%) of the viral membrane (Samji, 2009). HA is responsible for the virion binding to the sialic acid found on the cells in the upper respiratory tract. Cleavage of a single precursor is crucial for the activation of the membrane fusion potential which results in the initiation of infectivity (Garten and Klenk, 1999). A single arginine residue is the site of cleavage which occurs extracellularly by the protease human airway trypsin-like protease (HAT) and transmembrane protease serine S1 member 2 (TMPRSS2) enzymes (Gamblin and Skehel, 2010) (Bottcher et al., 2006). The nucleocapsid protein (NP) functions as a facilitator for integration and reverse transcription (Soszynska-Jozwiak et al., 2017). NP along with RNA polymerase makes up the 8 viral ribonuclease protein complexes, which is later arranged into an active virion particle (Soszynska-Jozwiak et al., 2017).
NA is a box-shaped homo-tetramer made up of four identical subunits help together on a thin 60-100 Å long stalk, which is attached to the viral membrane (Varghese and Colman, 1991). The active site and Ca2+ binding domain are found in the head of the NA. Ca2+ binding domain stabilises the enzyme structure at low pH to prevent the enzyme from losing its function (Lawrenz et al., 2010). NA catalyses the cleavage of α-ketosidic linkage between the sialic ac
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