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Author Topic: Viral Immune Modulators  (Read 2215 times)

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Offline Mishma

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Viral Immune Modulators
« on: July 25, 2012, 05:07:41 PM »
Viral immune modulators perturb the human molecular network by common and unique strategies

Andreas Pichlmair,    Kumaran Kandasamy,    Gualtiero Alvisi,    Orla Mulhern,    Roberto Sacco,    Matthias Habjan,    Marco Binder,    Adrijana Stefanovic,    Carol-Ann Eberle,    Adriana Goncalves,    Tilmann Bürckstümmer,    André C. Müller,    Astrid Fauster,    Cathleen Holze,    Kristina Lindsten,    Stephen Goodbourn,    Georg Kochs,    Friedemann Weber,    Ralf Bartenschlager,    Andrew G. Bowie,    Keiryn L. Bennett,    Jacques Colinge    & Giulio Superti-Furga
AffiliationsContributionsCorresponding author
Nature 487, 486–490 (26 July 2012) doi:10.1038/nature11289
Received 05 September 2011 Accepted 07 June 2012 Published online 18 July 2012

http://www.nature.com/nature/journal/v487/n7408/full/nature11289.html

Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms1, 2.

Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes3, 4. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies5, 6, 7, 8, 9, 10, 11.

Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system.

Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.
« Last Edit: July 27, 2012, 11:20:47 AM by Mishma »
2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline Ann

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Re: Viral Immune Modulators
« Reply #1 on: July 26, 2012, 03:45:49 AM »
Hi Mishma. I need you to read the two threads that are stickied at the top of this forum - the Welcome Thread and the one entitled A Request PLEASE READ THIS THREAD!!!.

When you read those two threads, you will realise that we require you to provide links to any articles you copy and paste into your posts. You have 48 hours in which you will be able to edit your post to add the links. If you miss the time-slot, please PM me the links so I can add them for you.

Thank you for your cooperation. :)

Ann
Condoms are a girl's best friend

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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline leatherman

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Re: Viral Immune Modulators
« Reply #2 on: July 26, 2012, 12:29:56 PM »
it's also nice netiquette to either give a synopsis of the article or your own comments/thoughts about the article since it interested you enough to post about it. ;)

what I read there was:
blah, blah, blah. there are even more obscure methods for a virus to break into the hosts cells. blah, blah, blah. :o maybe one day somebody can use this data to maybe develop another way to block viruses (like HIV I'm guessing) from getting in. blah, blah, blah. :D
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

Offline Mishma

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Re: Viral Immune Modulators
« Reply #3 on: July 26, 2012, 01:23:25 PM »
http://www.nature.com/nature/journal/v487/n7408/full/nature11289.html

Thank you both for your input. Since this was a journal article with its published date etc., I thought it would suffice. Unless a person has on line access to Nature (or is willing to pay for the individual article) the abstract is all there is. I was wrong. I apologize.

I will in the future also write a synopsis where I'll make it more accessable to a lay audience. Leatherman you are correct here as well. Surprisingly you got the gist of the abstract though and pretty much the takehome message-the nitty gritty sometimes gets in the way of the larger picture.

I worked for years with cytokines, the chemical messengers that cells use at short distances to communicate with one another. Now there is IL-1 to IL-35 and growing. Many of these have overlapping effects. Many of these are toxic at high doses and for the most part other than in culture conditions they didn't pan out or were toxic or quickly broken down. Examples include early work with IL-2 and erythropoietin, GM-CSF, and the list goes on and on. In addition, more than one cytokine is express in vivo. The important thing to remember is these are not hormones in the traditional sense but rather growth or inhibitory factors acting between individual cells.

What does this have to do with the abstract. Both deal with complex and yes esoteric stuff but cytokines like viral immune modulators form complex networks that affect the immune response. Cytokines are immune modulators that work from the outside in and immune modulators are host proteins that work within the cell.

The authors have used our knowledge of viral DNA ( genetic material that has made it's way into our own) and their protein products to identify host proteins that interact with them. The interactions are complex. Illustrations of these interactions are mind boggling to say the least.

So thanks Leatherman for the heads up and you have a good weekend as well. And so far as what I gleaned from the abstract-your interpretation is as good as mine.
2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline leatherman

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Re: Viral Immune Modulators
« Reply #4 on: July 26, 2012, 01:57:52 PM »
I will in the future also write a synopsis where I'll make it more accessable to a lay audience. Leatherman you are correct here as well. Surprisingly you got the gist of the abstract though and pretty much the takehome message-the nitty gritty sometimes gets in the way of the larger picture.
for a layperson who has spent 20+ yrs trying to learn enough about the disease I am infected with so that I and my doctor can properly care for me, sometimes it's hard to deal with nitty-gritty and the larger picture. All this biology stuff is so different from the business courses I took, or the computer work I do, or from the affairs of running a pet store (that I used to own). I've had to learn more than I ever wanted about biology and chemistry, but it sure has made me feel better through the yrs knowing what my meds are doing and what the new ones are going to do.

I often encourage people to dig into the package insert to really look at that information about what the med does and exactly what percentages of patients had which side effects - to find the nitty-gritty that pertains to them. While at other times, like with this information you posted, it's probably more important for the layperson (like me ;) ) to just understand the big picture - this isn't the "cure" but it's another possible stepping stone on the path to better meds or the cure. ;) :D

thanks for posting this info, the link, and for dumbing it down for me  ;D LOL
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

Offline Dr.Strangelove

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Re: Viral Immune Modulators
« Reply #5 on: July 26, 2012, 04:35:38 PM »
Ha, I happen to know the first and last author of that paper.
Anyway, I don't get too excited about this kind of fundamental research. It's going to take many years until this finds it's way into applied HIV research - if ever. And even more years until the first clinical trials.
Therefore, I'm much more interested in research news that that's further down the line; approaches that have been tested in a mouse model or other mammal etc.

Offline Ann

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Re: Viral Immune Modulators
« Reply #6 on: July 27, 2012, 04:41:56 AM »
http://www.nature.com/nature/journal/v487/n7408/full/nature11289.html

Thank you both for your input. Since this was a journal article with its published date etc., I thought it would suffice. Unless a person has on line access to Nature (or is willing to pay for the individual article) the abstract is all there is. I was wrong. I apologize.

I will in the future also write a synopsis where I'll make it more accessable to a lay audience. Leatherman you are correct here as well. Surprisingly you got the gist of the abstract though and pretty much the takehome message-the nitty gritty sometimes gets in the way of the larger picture.


Hey Mish, no worries. Thanks for adding the link.
Condoms are a girl's best friend

Condom and Lube Info  



"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

 


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