antiviral response promotes bacterial infection

[Guest guest]

Antiviral response promotes bacterial infection

Innate immune response to virus leaves mice more susceptible to

bacterial infection, study finds

[Published 10th October 2006 03:17 PM GMT]

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----------------------------------------------

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An innate immune response to viral infection can kill white blood

cells needed to fight off bacteria, according to a study published

online this week in PNAS. This effect could explain why

bacterial " superinfections " can take hold in the body more easily

when a viral pathogen is already present, the study authors say.

" Viral-bacterial synergism is something that is a significant

clinical issue in both human and veterinary medicine and we don't

have a detailed understanding of what's going on, " said

Czuprynski of the University of Wisconsin-Madison School of

Veterinary Medicine, who was not involved in the study.

Researchers led by A. Navarini and Mike Recher of the

University Hospital Zurich in Switzerland examined superinfection in

mice by first infecting them with an RNA virus called lymphocytic

choriomeningitis virus (LCMV) and then with the bacterium Listeria

monocytogenes. Three days later, the mice infected with both

pathogens showed 1000 times higher bacterial concentration in the

liver and spleen than did mice infected with bacteria only.

Since the mice showed susceptibility to bacterial superinfection in

the first three days, the authors examined key members of the early

innate immune response: white blood cells called granulocytes. In

humans, granulocyte number is the most important predictor of

susceptibility to bacterial infection, Navarini told The Scientist.

He and his colleagues found that granulocytes began undergoing

apoptosis about two days after viral infection and that granulocyte

numbers in bone marrow of mice infected with LCMV were considerably

below normal.

" There's probably some window of time here in which viral infection

leads to increased susceptibility to bacterial infection, and they're

providing a mechanistic explanation for why this might be occurring, "

Czuprynski said.

The researchers next looked for antiviral factors that might be

responsible for granulocyte death. They found that levels of type I

interferon -- a cytokine known to become up-regulated in response to

most viruses, including LCMV -- inversely correlated with levels of

granulocytes. To see if there was a causal connection, the

researchers infected mice lacking type I interferon receptors with

LCMV. These mice did not show granulocyte cell death or sensitivity

to L. monocytogenes infection - demonstrating that type I interferon

activity is required for virus-induced granulocyte death.

" This link to the interferon is really interesting, " said

McCullers of St. Jude Children's Research Hospital in Memphis, who

was not involved in the study. " That, to me, is the important part of

the paper. "

It's not yet clear if this mechanism will underlie other cases of

bacterial superinfection after viral disease, Czuprynski told The

Scientist, but, because type I interferon activation is a generalized

body response to viral infection, " this might be something that

happens with other viral agents as well, " he said.

" All agents causing high interferon type I levels are in our opinion

likely to cause such effects and facilitate superinfection, " Navarini

told The Scientist in an Email.

According to McCullers, " it's going to take a little work to

generalize it to human viruses. Influenza, for example, causes an

increase in human granulocyte number and so probably does not

encourage bacterial infection through this mechanism, but " it might

be a very reasonable model for HIV, " McCullers told The Scientist.

Researchers will " have to apply it to each virus in turn and see if

it fits. "

Lee

mphillips@...

Links within this article:

C. Holding, " Evolution of innate immunity, " The Scientist, July 8,

2004.

http://www.the-scientist.com/article/display/22271/

<http://www.the-scientist.com/article/display/22271/>

J.F. , " Renewing the Fight Against Bacteria, " The Scientist,

March 4, 2002.

http://www.the-scientist.com/article/display/12902/

<http://www.the-scientist.com/article/display/12902/>

Navarini et al., " Increased susceptibility to bacterial

superinfection as a consequence of innate antiviral responses, " PNAS,

published online October 9, 2006.

http://www.pnas.org/ <http://www.pnas.org/>

Czuprynski

http://www.vetmed.wisc.edu/VetWeb/Default.aspx?

<http://www.vetmed.wisc.edu/VetWeb/Default.aspx?>

inject=bio & uid=czuprync

L. Malmgaard et al., " Promotion of alpha/beta interferon induction

during in vivo viral infection through alpha/beta interferon

receptor/STAT1 system-dependent and -independent pathwaysm, " Journal

of Virology, May 2002.

http://www.the-scientist.com/pubmed/11932417

<http://www.the-scientist.com/pubmed/11932417>

C.Q. Choi, " How viruses interfere with interferon, " The Scientist,

October 1, 2006.

http://www.the-scientist.com/2006/9/1/66/1/

<http://www.the-scientist.com/2006/9/1/66/1/>

McCullers

http://www.stjude.org/faculty/0,2512,407_2030_4027,00.htm

<http://www.stjude.org/faculty/0,2512,407_2030_4027,00.html>

[Guest guest]

This is both fascinating and scary!

Wouldn't it be nice if one day doctors could do a routine set of

tests on all patients to find out what types of chemical deficits

each person has. I would think insurance companies would love

this. Wonder why insurance companies don't fund more research.

--- In , Doris and Steve <sjsmith@...>

wrote:

>

> Antiviral response promotes bacterial infection

>

> Innate immune response to virus leaves mice more susceptible to

> bacterial infection, study finds

>

> [Published 10th October 2006 03:17 PM GMT]

>

>

> ------------

> ----------------------------------------------

> ----------

>

> An innate immune response to viral infection can kill white blood

> cells needed to fight off bacteria, according to a study published

> online this week in PNAS. This effect could explain why

> bacterial " superinfections " can take hold in the body more easily

> when a viral pathogen is already present, the study authors say.

>

> " Viral-bacterial synergism is something that is a significant

> clinical issue in both human and veterinary medicine and we don't

> have a detailed understanding of what's going on, " said

> Czuprynski of the University of Wisconsin-Madison School of

> Veterinary Medicine, who was not involved in the study.

>

> Researchers led by A. Navarini and Mike Recher of the

> University Hospital Zurich in Switzerland examined superinfection

in

> mice by first infecting them with an RNA virus called lymphocytic

> choriomeningitis virus (LCMV) and then with the bacterium Listeria

> monocytogenes. Three days later, the mice infected with both

> pathogens showed 1000 times higher bacterial concentration in the

> liver and spleen than did mice infected with bacteria only.

>

> Since the mice showed susceptibility to bacterial superinfection in

> the first three days, the authors examined key members of the early

> innate immune response: white blood cells called granulocytes. In

> humans, granulocyte number is the most important predictor of

> susceptibility to bacterial infection, Navarini told The Scientist.

> He and his colleagues found that granulocytes began undergoing

> apoptosis about two days after viral infection and that granulocyte

> numbers in bone marrow of mice infected with LCMV were considerably

> below normal.

>

> " There's probably some window of time here in which viral infection

> leads to increased susceptibility to bacterial infection, and

they're

> providing a mechanistic explanation for why this might be

occurring, "

> Czuprynski said.

>

> The researchers next looked for antiviral factors that might be

> responsible for granulocyte death. They found that levels of type I

> interferon -- a cytokine known to become up-regulated in response

to

> most viruses, including LCMV -- inversely correlated with levels of

> granulocytes. To see if there was a causal connection, the

> researchers infected mice lacking type I interferon receptors with

> LCMV. These mice did not show granulocyte cell death or sensitivity

> to L. monocytogenes infection - demonstrating that type I

interferon

> activity is required for virus-induced granulocyte death.

>

> " This link to the interferon is really interesting, " said

> McCullers of St. Jude Children's Research Hospital in Memphis, who

> was not involved in the study. " That, to me, is the important part

of

> the paper. "

>

> It's not yet clear if this mechanism will underlie other cases of

> bacterial superinfection after viral disease, Czuprynski told The

> Scientist, but, because type I interferon activation is a

generalized

> body response to viral infection, " this might be something that

> happens with other viral agents as well, " he said.

>

> " All agents causing high interferon type I levels are in our

opinion

> likely to cause such effects and facilitate superinfection, "

Navarini

> told The Scientist in an Email.

>

> According to McCullers, " it's going to take a little work to

> generalize it to human viruses. Influenza, for example, causes an

> increase in human granulocyte number and so probably does not

> encourage bacterial infection through this mechanism, but " it might

> be a very reasonable model for HIV, " McCullers told The Scientist.

> Researchers will " have to apply it to each virus in turn and see if

> it fits. "

>

> Lee

> mphillips@

>

> Links within this article:

>

> C. Holding, " Evolution of innate immunity, " The Scientist, July 8,

> 2004.

> http://www.the-scientist.com/article/display/22271/

> <http://www.the-scientist.com/article/display/22271/>

>

> J.F. , " Renewing the Fight Against Bacteria, " The Scientist,

> March 4, 2002.

> http://www.the-scientist.com/article/display/12902/

> <http://www.the-scientist.com/article/display/12902/>

>

> Navarini et al., " Increased susceptibility to bacterial

> superinfection as a consequence of innate antiviral responses, "

PNAS,

> published online October 9, 2006.

> http://www.pnas.org/ <http://www.pnas.org/>

>

> Czuprynski

> http://www.vetmed.wisc.edu/VetWeb/Default.aspx?

> <http://www.vetmed.wisc.edu/VetWeb/Default.aspx?>

> inject=bio & uid=czuprync

>

> L. Malmgaard et al., " Promotion of alpha/beta interferon induction

> during in vivo viral infection through alpha/beta interferon

> receptor/STAT1 system-dependent and -independent pathwaysm, "

Journal

> of Virology, May 2002.

> http://www.the-scientist.com/pubmed/11932417

> <http://www.the-scientist.com/pubmed/11932417>

>

> C.Q. Choi, " How viruses interfere with interferon, " The Scientist,

> October 1, 2006.

> http://www.the-scientist.com/2006/9/1/66/1/

> <http://www.the-scientist.com/2006/9/1/66/1/>

>

> McCullers

> http://www.stjude.org/faculty/0,2512,407_2030_4027,00.htm

> <http://www.stjude.org/faculty/0,2512,407_2030_4027,00.html>

>

>

>