How does an enteric virus survive the stomach on its way to the
intestine when it's partially dismantled by an acidified endosome?

Hello -

The enterovirus category is fairly large and comprised of many viruses
which have all been studied to different extents.  There does not
appear to be an overall consensus on how the genetic material gets
from the virus into the cytosol of the cell.  The two main theories
(and a combination theory) are:
1) the virus is internalized into the endosome - the endosome
acidifies which leads to changes in the shape of viral proteins,
causing them to form pores (or "poke holes" if you will) into the
endosome which the virus uses to insert the genetic material into the
cytosol.
2) the virus actually inserts it's genetic material into the cell at
the time of binding to the surface (this would be similar to how other
viruses and bacteriophages (bacterial viruses) function) and the
endosomal virus particles are either remnants left over after
insertion, or represent "failed" virus
3) a combination of the two approaches - suggesting that the viruses
begin to insert their genetic material at the time of binding to the
cell, and that some viruses are able to increase their rate of
insertion by forming pores under the acidic conditions of the endosome
(thus, they penetrate even without acidic conditions, but do so much
more readily with acidic endosomes).

I was unable to find a good site on the free internet as a reference -
the following references are all available through PubMed (and should
be available at your local medical school, large college, and maybe
even your library):

It appears as though the very acidic conditions of the endosome are
necessary for the release of viral genetic material into the cytosol
of the cell:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2857762&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11576449&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10325536&dopt=Abstract

This is likely due to alterations in the structure of viral proteins
exposed after the virus is uncoated - certain proteins (such as the
endosomal native proteins) thrive at low pH (acidic) conditions.  One
prototypical virus for study is adenovirus (while not an enterovirus)
- adenovirus uses it's "penton base protein" to open holes in the
endosomal membrane, thus allowing penetration into the cytosol -
enough holes in the membrane likely lead to endosomal rupture (this
can also be seen with some bacteria):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9445036&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7559769&dopt=Abstract

The fact that the endosomal passage changes the virions into
"subinfectious particles" that are devoid of RNA, suggests that the
RNA is exported out of the endosome, and the most likely candidate
would be pore-forming proteins:
a paper which suggests, but does not prove this:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9722884&dopt=Abstract

Another approach to this same question concludes that the virus
unloads it's genetic cargo at the surface of the cell, and only
incompetent virus becomes internalized into the endosomes (thus, this
paper would suggest that endosomal virions are artifact of failed
infections - or are the remnants of virions that have already unloaded
their contents at the surface of the cell), although this paper cannot
address why the acidic conditions of the endosome appear to be
necessary for the unloading of the genetic material:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9527481&dopt=Abstract

another paper which suggests that acidification of the endosome is not
necessary for endosomal release of viral genetic material (although,
when not acidified, the release of genetic material was greatly
diminished):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10601662&dopt=Abstract


Let me know if you have further questions.

synarchy

Search
PubMed: enterovirus endosome escape
enterovirus endosome
poliovirus endosome
picornavirus endosome
endosome escape
endosome acidification

Greetings Akdelta5:

The only reference I could locate was this:

"After the virus is partially dismantled by the acidic conditions
within the endosome, it escapes into the cytoplasm, and injects its
cargo of DNA into the cell’s nucleus. You may be wondering: If the
virus coat is "partially dismantled" in the acidified endosome, why
isn’t the virus stripped totally naked by the acidic conditions in the
stomach? I could wave my hands and make up a story about how the virus
may be protected within a clump of food as it transits the stomach,
but the truth is,nobody has a clue as to how adenovirus accomplishes
this amazing feat."
From http://216.239.51.104/search?q=cache:LpVMK72j-wEJ:medicine.jbpub.com/infectiousdisease/pdf/som20828_ch04.pdf+%22enteric+virus%22+%22partially+dismantled%22+%22acidified+endosome%22&hl=en&ie=UTF-8

I would have answered with this information but I wasn't able to
locate a second source.  I hope another Researcher will be able to
confirm the fact I located.

Best regards,
journalist-ga


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