The multi basic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets

[tetano]

J Virol. 2012 Jan 25. [Epub ahead of print]
The multi basic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets.
Schrauwen EJ, Herfst S, Leijten LM, van Run P, Bestebroer TM, Linster M, Bodewes R, Kreijtz JH, Rimmelzwaan GF, Osterhaus AD, Fouchier RA, Kuiken T, van Riel D.
Source

National Influenza Center and Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.
Abstract

The route by which highly pathogenic avian influenza (HPAI) H5N1 virus spreads systemically, including the central nervous system (CNS), is largely unknown in mammals. Especially the olfactory route, which could be a route of entry into the CNS, has not been studied in detail. Although the multi basic cleavage site (MBCS) in the HA of HPAI H5N1 viruses is a major determinant of systemic spread in poultry, the association between the MBCS and systemic spread in mammals is less clear. Here we determined the virus distribution of HPAI H5N1 virus in ferrets in time and space-including along the olfactory route-and the role of the MBCS in systemic replication. Intranasal inoculation with wild type H5N1 virus revealed extensive replication in the olfactory mucosa from where it spread to the olfactory bulb and the rest of the CNS, including the cerebral spinal fluid (CSF). Virus spread to the heart, liver, pancreas and colon was also detected, indicating hematogenous spread. Ferrets inoculated intranasally with H5N1 virus lacking a MBCS demonstrated respiratory tract infection only. In conclusion, HPAI H5N1 virus can spread systemically via two different routes, the olfactory and hematogenous routes in ferrets. This systemic spread was dependent on the presence of the MBCS in HA.

PMID:
22278228
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22278228

 

[Vibrant62]

Re: The multi basic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets

A good study for anyone trying to understand why H5 can be so lethal. Also important to understand is that H5 viruses pick up and drop additional bases in the cleavage site easily (increasing or decreasing the length of the cleavage chain). Low path viruses can become high path ones very easily and vice versa just during the natural course of evolution within its host.

There are many factors that affect the virulence of a virus; the number of tissue types it can infect is one of these, and this is closely linked to the cleavage site configuration. All H5N1 currently lacks is the ability to transmit eadily, and this may have something to do with its current ability (or lack thereof) to enter respiratory secretions.