Influenza occurs all over the world, with an annual global attack rate estimated at 5 – 10% in adults and 20 – 30% in children. Influenza is associated with considerable economic burden arising from health-care costs, lost days of work or education, and general social disruption across all age groups. Secondary bacterial pneumonia is a frequent complication of influenza infection, particularly in elderly people and individuals with certain chronic diseases, resulting in a significant level of morbidity and mortality
Inﬂuenza viruses are part of the family Orthomyxoviridae, which comprises Inﬂuenza A virus, Inﬂuenza B virus, Inﬂuenza C virus based on the antigenicity of viral nucleotide and M proteins. Type B and C virus infect only humans, while type A can infect not only humans but also birds, pigs, and horses. Influenza viruses are enveloped particles with a cylinder shape having a diameter of 80 to 120 nm. Type B viruses have the longest genome (≈14600 nucleotides), followed by A (≈13600 nucleotides) and then C (≈12900 nucleotides. The genome of Influenza B virus, consists of eight negative-strand RNA segments, which encode 11 proteins. Of these, nine are also found in influenza A virus: three RNA-dependent RNA polymerase (RdRp) subunits (PB1, PB2, and PA), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix protein (M1), and two nonstructural proteins (NS1 and NS2) (Figure 1). Two proteins, NB and BM2, are unique to influenza B virus. NB is encoded by RNA segment 6, which also encodes NA, while BM2 is encoded by segment 7.1
Eight single-stranded RNA segments are also called as “segmented genome” or “split genome,” because it is split into eight segments each encoding at least one protein. Envelope glycoproteins HA and neuraminidase NA studded in the envelope plays an important role in nomenclature of influenza virus. HA is distributed evenly on the surface of virions. It accounts for about 25% of viral protein and is responsible for the attachment and subsequent penetration of viruses into cells. A certain strain can also be described as the combination of one HA and one NA subtype: for example, H1N1 or H5N1 strain. However, so far only H1N1 and H3N2 subtypes along with influenza B virus are known to cause seasonal flu epidemics; for instance, H1N1 and H3N2 subtypes and influenza B virus are responsible for the 2013 flu epidemics. In nomenclature of influenza virus in addition to the multiplicity of subtypes, the country (city) and year of isolation are explicitly indicated. For instance, A/Puerto Rico/8/1934 (H1N1) refers to the virus isolated in Puerto Rico in 1934 that is classified as type A and an H1N1 subtype. M2 protein, which acts as an ion channel whereas matrix protein M1 is attached to the inner leaflet of the lipid bilayer. Inside the envelope, eight segmented RNAs (ie, vRNAs) are present each of which is encompassed by NP (i.e, vRNPs). Inside of the particles, RdRp is associated to vRNPs. The M and NS genes of all inﬂuenza viruses and the NA gene of type B virus encodes two proteins each via alternative splicing. Inﬂuenza B contains gene for nine structural and two nonstructural proteins. The genes encoding HA and NA, are highly conserved among influenza strains, still another mechanism of viral protein synthesis is represented by the inﬂuenza B virus. Inﬂuenza B virus HAs bind to oligosaccharide containing terminal sialic acids. The amino acid residues in HA1 that contact the terminal sialic acids are highly conserved among the diﬀerent HA subtypes. The three-dimensional structure of type A and B viruses shows 28% homology, the overall folding patterns of their NAs are almost identical. The dimeric, integral membrane protein NB is unique to type B viruses. NB contains structural features similar to those of the M2 protein and was therefore thought to function as an ion channel. However, reverse genetics studies revealed that it is dispensable for virus replication invitro. Unlike other viruses, influenza replication occurs in the nucleus. Influenza virus enters the cell via recognition of the cellular receptor, a sialic acid. The engagement of the HA timer to a sialic acid moiety of glycan on the cell membrane triggers endocytosis.
An influenza pandemic is a rare but recurrent event. Influenza B viruses cause the same spectrum of disease as influenza A but do not cause pandemics. This property may be a consequence of the limited host range of the virus – humans and seals – which limits the generation of new strains by reassortment. The virus causes significant morbidity: in the US in 2008, approximately one-third of all laboratory confirmed cases of influenza were caused by influenza B. Consequently the seasonal trivalent influenza vaccine contains an influenza B virus component. Influenza virus is transmitted primarily by droplets or respiratory secretions of infected persons. Protection is conferred by serum antibodies, where HA is the major antigenic target of neutralizing antibodies. However, due to antigenic drift and antigenic shift, the protective effect of antibody induced by one strain may be reduced or lost as a function of time, resulting in individuals being relatively or completely unprotected against the new strains in circulation. Vaccines available are categhorised into inactivated and live attenuated vaccines. Inactivated vaccines are three types, the whole virus vaccines, split virus vaccines, and subunit vaccines. In split virus vaccines, the virus is disrupted by a detergent. In the recent years vaccines production has developed with the use of, mammalian cells for vaccine production, adjuvants, and reverse genetics. Live, attenuated influenza vaccines have been based on a temperature-sensitive variant vaccine virus strains that replicate well in the nasopharynx but poorly in the lower respiratory tract.
Therapeutic choices has two classes of FDA-approved antivirals targeting the viral matrix 2 (M2) ion channel protein (amantadine or rimantadine) or the sialidase active site of the viral NA protein (oseltamivir, zanamivir, or peramivir). M2 inhibitors are not efficient against Influenza B virus. On the other hand, NA blockers (oseltamivir and zanamivir, and more recently peramivir and laninamivir) are efficient against Influenza B virus however the emergence of drug-resistant strains is currently increasing. WHO NA blockers as the first-line treatment for those requiring antiviral therapy, as most of the currently circulating viruses are resistant to the M2 inhibitors. For high-risk individuals, NA inhibitors should be administered early in the course of the disease. Among NA inhibitors, oseltamivir is most widely used, with accumulated safety data that include treatment in young children and pregnant women. Early and widespread use of NA inhibitors has been associated with reduced hospitalization and mortality, particularly during the 2009 pandemic.