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References 91

Synthesis of viral RNA and viral proteins

The RNPs are transported to the nucleus, where the polymerase complex binds to viral RNA, cleaves viral RNA by its endonuclease activity, and simultaneously leads to elongation. The production of viral RNA is limited by the NP in favour of mRNA. Both are transported to the cytoplasm, where viral proteins are generated at the ribosome. Part of the viral mRNA is spliced by cellular enzymes so that finally viral proteins, such as M1 and NS2, can be synthesised without any further cleavage. Some of the newly synthesised viral proteins are transported to the nucleus where they bind to viral RNA to form RNPs. Other newly synthesised viral proteins are processed in the endoplasmic reticulum and the Golgi apparatus where glycosylation occurs. These modified proteins are transported to the cell membrane where they stick in the lipid bilayer. When they reach a high enough concentration at the plasma membrane, RNPs and M1 proteins aggregate and condense to produce the viral particle. Finally, the particle is extruded from the membrane and will be liberated by the neuraminidase activity.

The time from entry to production of new virus is on average 6 h.

Shedding of the virus and infectivity

Immunohistological pictures show that foci of virus-producing cells are clustered in the mucous layer of the respiratory tract, in the gut and even in endothelial layers, myocardium and brain. Within nasal secretions, millions of virus particles per ml are shed, so that a 0.1 µl aerosol particle contains more than 100 virus particles. A single HID (human infectious dose) of influenza virus might be between 100 and 1,000 particles. At least during the early course of influenza infection, the virus can be found also in the blood and in other body fluids.

Infectivity of influenza virus particles is preserved depending on temperature, pH and salinity of the water, and UV irradiation. At 4°C, the half-life of infectivity is about 2-3 weeks in water. Due to the conformation of the lipid bilayer, survival under normal environmental conditions should be shorter.

Infectivity of the influenza virus particle is easily inactivated by all alcoholic disinfectants, chlorine and aldehydes. As far as is known, temperatures above 70°C will destroy infectivity in a few seconds.

References

Nicholson KG, Webster RG, Hay AJ. Textbook of Influenza. Blackwell Science, Oxford, 1998.

Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their Replication. In: Fields Virology fourth edition, Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1487-1531

Wright PF, Webster RG. Orthomyxoviruses. In: Fields Virology fourth edition, Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1533-1579

Special reference

Wetherall NT, Trivedi T, Zeller J, Hodges-Savola C, McKimm-Breschkin JL, Zambon M, Hayden FG. Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network. J Clin Microbiol 2003; 41: 742-750. Full text at http://jcm.asm.org/cgi/content/full/41/2/742?view=long&pmid=12574276