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Characteristics
Influenza virus belongs to the orthomyxoviridae family. Influenza virus have segmented negative-sense single stranded RNA molecules, which are eight in number. Its an enveloped virus which is made up of proteins, glycoproteins, and lipid bilayer. Helical in symmetry.
Orthomyxoviruses
HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex
M1 protein
Human epidemics
Antigenic changes Segmented genome Amantadine, rimantidine Zanamivir
Yes
Shift, drift Yes Sensitive Sensitive
Yes
Drift Yes No effect Sensitive
No(sporadic)
Drift Yes No effect
Surface glycoproteins
Influenza Biology
HA attaches to the membrane of epithelial cells via sialic acid-galactose H+ ion passes through the viral M2 matrix ion protein channels Fusion of endosome membrane and viral membrane; release of RNA and NP After attachment endocytosis occurs
M2 HA
Acidification of the core leads to conformation changes in HA making it a fusogen Inside the endosome pH gets lowered
Influenza Biology
Mode of action of H1 N1
Virus infects upper respiratory system
Virus adheres to epithelial cells (receptor mediated endocytosis) Action of lysosome on endosome
When endosome pH decreases, haemagglutine molecule undergoes conformational change. The hydrophobic end of haemagglutine spring outward & extends towards the membrane of endosome.
Mode of action of H1 N1
Apoptosis
As a result, there is reduced clearance of infectious agents from the respiratory tract. Gaps in the protective epithelium provide other pathogens with access to other cells.
Antigenic Drift
Antigenic Shift
Source: http://www.globalsecurity.org/security/ops/hsc-scen-3_flu-antigenic.htm
Treatment Treatment
Vaccine
Ex. Baxter vaccine
(inactivated virus vaccine)
Antiviral Drugs
Neuraminidase inhibitors
Ex. Oseltamivir :TAMIFLU Zanamivir :RELENAZA
Influenza Vaccines
Influenza Vaccines
Inactivated vaccine (TIV)
flu shot (injection) Purified virus chemically inactivated by formalin or propiolactone trivalent (three strains; usually A/H1N1, A/H3N2, and B) non-replicating virus contain much more antigen than live vaccines works by putting into the bloodstream those parts of three strains of flu virus that the body uses to create antibodies
nasal spray (FluMist) Live virus, completely devoid of pathogenicity provide continuous antigenic stimulation works by inoculating against those same three strains that have been genetically modified to minimize symptoms of illness. Each of the three strains is a reassortant of internal proteins of a master donor virus (MDV) that contains the CA and TS phenotypes surface proteins (HA, NA) are from wild-type influenza virus.
SEED VIRUS: a hybrid is formed which contains the inner components of the laboratory strain, and the outer components of the pandemic strain
Millions of specially - prepared chicken eggs are used to produce the vaccine. Throughout the year, fertilized eggs are delivered to the manufacturer. Each egg is injected with the working seed. The eggs are incubated for several days to allow the virus to multiply. After incubation, the virus loaded fluid is harvested.
Limitations
A limitation of current vaccines is that the antigenic regions of HA are highly susceptible to continuous mutation in circulating epidemic virus strains. Thus, the currently available influenza vaccines need to be updated every year to match the antigenicity of the virus strains that are predicted to circulate in the next season. However, current vaccines would not be effective in preventing the spread of a new pandemic strain containing a substantially different HA protein. Therefore, new approaches are being investigated to develop broadly crossprotective vaccines, focused primarily on type A influenza viruses
Challenges
Non egg based production Targeting generation of virus specific CTLs Increasing immunogenicity and adjuvants Rapid production Dosage
References
Novel vaccines against influenza viruses: Virus Research, Volume 162, Issues 12, December 2011, Pages 31-38. S.M. Kang, J.M. Song, R.W. Compans The Influenza Virus Enigma: Cell, Volume 136, Issue 3, 6 February 2009, Pages 402-410 Rachelle Salomon, Robert G. Webster The 2009 A (H1N1) influenza virus pandemic: A review: Vaccine, Volume 28, Issue 31, 12 July 2010, Pages 4895-4902 Marc P. Girard, John S. Tam, Olga M. Assossou, Marie Paule Kieny