particle to pfu ratios

Steven Enkemann enkemans at dc37a.nci.nih.gov
Mon Jul 31 19:01:09 EST 1995


 
> 
> Hi Steven,
> 
> would you predict that bigger viruses characteristically have lower
> particle/pfu ratios than very small viruses?
> 
> Regards, Kevin.
> -- 

   Not at all.  The pfu to particle ratio depends on all the factors I
mentioned.  But even in a perfect viral world where all virions were
complete and their were no host defense mechanisms the answer would still
be no.
   Do you really mean smaller  viruses or less complex viruses?  In
neither case is there a direct correlation with infectivity by complete
virions.  Clearly large and complex viruses such as the Pox virus or
Herpes Simplex are very efficient at initiating an infection once they get
into a cell.  They possess most of the biochemical machinery necessary for
viral replication and their infectious centers are visible as discrete
bodies within infected cells.  Once inside, the infection has a great
chance of succeeding.  The trade-off however, is that they also possess
more foreign proteins that act as immunogens and the complexity results in
a greater chance of an assembly error that yields an incomplete particle.
Unfortunately, in a plaque assay it is very difficult to separate host
mechanisms that act before a virus enters a cell from viral shortcomings
that manifest themselves only after the virus has entered the cell. 
   The picornaviruses are very small and Œsimple¹ viruses.  Yet they are
probably also great at initiating an infection once they enter a cell. 
The reason here is that their genomes are in essence messenger RNAs and
the initial event in their lifecycle is to be translated by a ribosome. 
Since cells are full of ribosomes this is very likely to occur.  In fact
their genomes alone, removed from the intact virion and transfected into
cells are very infectious.
   The key step is the nature of the initial event in the life cycle of
the virus that begins the infectious process.  Lets skip the initial
events of adsorption and penetration.  I consider difficulty at those
stages to be part of the host¹s natural defense mechanism.  The initial
virus directed biochemical event that starts the process of producing new
virus particles.  If this event relies on viral proteins and those
proteins are in limited supply the biochemical process may never occur. 
Retroviruses are good examples of this.  Their initial event, conversion
of their genome to DNA requires the viral genome, a transfer RNA molecule
for a primer, and reverse transcriptase.  All of these components are in
limiting supply at the initial site of infection.  The most limiting is
the genome which is present in two copies per virion.  If these components
don¹t  come together and stay together within the cell long enough to
produce a double stranded DNA copy  of the genome the infection fails.

Steven A. Enkemann PhD.



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