02/19/2019

How can HIV be inhibited

By Live Dr - Mon Jul 04, 12:55 pm

Researchers at Case Western Reserve University School of Medicine have discovered a long-sought cellular factor that works to inhibit HIV infection of myeloid cells, a subset of white blood cells that display antigens and hence are important for the body’s immune response against viruses and other pathogens.

The factor, a protein called SAMHD1, is part of the nucleic acid sensing machinery within the body’s own immune system. It keeps cells from activating immune responses to the cells own nucleic acids, thus preventing certain forms of autoimmunity from developing.

SAMHD1 factor, researchers have found, can also sense and interfere with infection of myeloid cells, such as macrophages and dendritic cells, with HIV-1 and related immunodeficiency viruses. As such, SAMHD1 prevents the synthesis of virus copies in these cells, according to research led by Jacek Skowronski, PhD, a professor in the Department of Molecular Biology and Microbiology and member of the Center for AIDS Research at the Case Western Reserve University School of Medicine.

The findings appear in a manuscript published in the June 30 issue of Nature featuring Dr. Skowronski as the paper’s senior author. The research was carried out in his lab at Case Western Reserve in collaboration with a research group led by Michael P. Washburn, PhD, at the Stowers Institute for Medical Research in Kansas City.

This issue of Nature also carries an independent report by a team from France headed by Monsef Benkirane, PhD, that identifies SAMHD1 as a factor that limits HIV growth in myeloid cells. The research broadens the understanding of how the immune system of the infected people handles HIV, and how HIV evades the immune system’s response.

“The identification of SAMHD1 and its function may help to explain why some infected individuals can control HIV infection better than others,” Dr. Skowronski says. “Ultimately, it could also provide a basis for conceiving of new therapies and treatment approaches to block HIV infection and/or its replication in infected individuals, and to stimulate body’s own immune response to HIV.”

Prior to this research the normal function of SAMHD1 was thought to be the prevention of the inappropriate activation of a class of the anti-viral responses mediated by production of anti-viral factors termed interferons, in the absence of virus infection. Mutations in SAMHD1, as well as two other cellular genes that encode nucleases, TREX1 and RNAse H2, cause a condition called Acairdi-Goutieres syndrome (AGS). The condition mimics congenital viral infection, and is due to unwarranted induction of the immune system’s interferons in the absence of the virus. SAMHD1 and other AGS-causing cell proteins work to dispose cellular nucleic acid debris, thereby preventing inappropriate activation of the interferon system.

In the work described in the Nature manuscript, the researchers led by Dr. Skowronski discovered that in addition to preventing inappropriate autoimmune responses such as those seen in AGS, SAMHD1 possesses the ability to inhibit infection of myeloid cells by HIV by effectively interfering with the production of viral nucleic acids. Through this action SAMHD1 may prevent efficient activation of immune responses to HIV-1 virus in infected individuals, Dr. Skowronski explains.

The research also shows HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) are able to overcome the protective mechanism within myeloid cells by using the protein Vpx they encode, to dispose of SAMHD1, thereby allowing infection with these viruses. Interestingly, viruses possessing Vpx, such as HIV-2, are much less pathogenic than HIV-1. This could be because by being able to establish infection in myeloid cells they provoke much more robust immune responses that HIV-1 does, since HIV-1 can not infect these cells efficiently, Dr. Skowronski says.

As a result, “One might expect that manipulation of SAMHD1 function in the context of HIV-1 infection may lead to more robust immune response to this virus” according to Dr. Skowronski.

Moving forward, researchers will focus on better understanding the molecular pathway SAMHD1 uses to inhibit HIV-1 infection. They will likewise strive to learn more about how SAMHD1 shapes the development of AIDS in HIV-infected individuals, Dr. Skowronski says.

Link:Sciencedaily.com

142 Comments

Comments 101 - 142 of 142First« PrevNext »Last
  1. Really enjoyed this blog article.Much thanks again. Fantastic.

  2. Undoubtedly advantageous mindset, thank you for sharing with us.. Liking the posting.. all the best Enjoying the posting.. bless you Value the posting you given..

  3. I must show some appreciation to this writer for bailing me out of such a dilemma. As a result of browsing through the world wide web and finding things which were not helpful, I figured my entire life was over. Living without the presence of approaches to the issues you have sorted out by way of your main blog post is a critical case, and ones that might have badly affected my entire career if I hadn’t encountered the website. Your own personal know-how and kindness in controlling all areas was helpful. I’m not sure what I would have done if I had not come upon such a step like this. I’m able to at this point look forward to my future. Thank you so much for the skilled and result oriented guide. I won’t hesitate to suggest your web site to any individual who needs to have assistance on this problem.

  4. My wife and i have been very glad when Chris managed to round up his homework using the ideas he got from your weblog. It’s not at all simplistic to just choose to be giving out instructions that the others have been trying to sell. And we acknowledge we need the blog owner to appreciate because of that. The specific explanations you have made, the simple site menu, the relationships your site aid to engender – it is everything overwhelming, and it is making our son in addition to the family consider that this idea is amusing, and that’s incredibly vital. Thanks for the whole thing!

  5. Understanding whаА аЂаt you un?erstand no? out of

  6. I not to mention my guys were found to be examining the nice recommendations on your site while immediately got a horrible suspicion I had not expressed respect to the site owner for them. All the young men were definitely certainly excited to learn them and have now clearly been tapping into those things. Appreciate your simply being well considerate and also for utilizing some tremendous issues most people are really desperate to be informed on. Our own honest apologies for not expressing appreciation to sooner.

  7. I am also writing to make you understand of the cool encounter my girl had reading through your web site. She noticed so many issues, not to mention how it is like to have an ideal helping nature to have men and women just comprehend specified very confusing topics. You undoubtedly exceeded visitors’ expected results. Thank you for presenting the powerful, healthy, educational not to mention easy guidance on your topic to Lizeth.

  8. Thank you so much for providing individuals with an exceptionally brilliant possiblity to read critical reviews from here. It is usually so cool and jam-packed with a lot of fun for me and my office friends to search your blog no less than three times in a week to see the latest guides you have. Not to mention, I am also at all times contented concerning the mind-boggling information served by you. Certain 1 facts in this post are really the most impressive I’ve had.

  9. You have remarked very interesting details ! ps nice internet site. аАа’аАТ‚аЂТ˜Tis a sharp medicine, but it will cure all that ails you. аАа’аАТ‚б‚Т€Т last words before his beheadding by Sir Walter Raleigh.

  10. Great website! It looks very expert! Maintain the great work!

  11. Thank you for your article.Much thanks again. Really Cool.

  12. It as not that I want to replicate your web site, but I really like the style. Could you let me know which design are you using? Or was it especially designed?

  13. I precisely wished to thank you so much once again. I am not sure the things I would have taken care of without the type of tricks shown by you about such concern. It has been an absolute alarming problem in my circumstances, nevertheless taking a look at a new specialised style you dealt with that forced me to jump with happiness. I will be thankful for this information and as well , sincerely hope you are aware of a great job you’re carrying out training the mediocre ones using a site. I’m certain you have never encountered any of us.

  14. I truly wanted to write down a quick comment in order to thank you for those amazing tips and tricks you are posting at this site. My rather long internet look up has at the end been paid with high-quality facts and techniques to talk about with my colleagues. I would believe that most of us website visitors are very fortunate to live in a wonderful community with very many marvellous people with beneficial advice. I feel quite privileged to have encountered your webpage and look forward to many more thrilling minutes reading here. Thank you once again for everything.

  15. Thanks so much for providing individuals with such a splendid chance to read from this web site. It’s usually very pleasing and also stuffed with fun for me and my office colleagues to search your web site on the least 3 times in a week to read the fresh stuff you will have. And indeed, I am just actually contented with all the amazing points you give. Some 2 points in this posting are undoubtedly the most effective I have had.

  16. I together with my pals ended up reading through the good guides from your web blog then immediately came up with a horrible feeling I never expressed respect to you for those strategies. The women came for that reason glad to see all of them and have now very much been taking advantage of them. Many thanks for being simply considerate and for obtaining these kinds of wonderful subjects most people are really desperate to understand about. Our own sincere regret for not expressing appreciation to earlier.

  17. This very blog is without a doubt interesting and besides diverting. I have picked up helluva useful stuff out of this amazing blog. I ad love to go back every once in a while. Thanks!

  18. I actually wanted to send a note in order to thank you for all the pleasant tips and hints you are placing at this website. My time intensive internet look up has at the end of the day been paid with reliable tips to share with my good friends. I ‘d repeat that many of us readers are undeniably lucky to exist in a wonderful network with so many wonderful professionals with very helpful plans. I feel really lucky to have encountered your webpage and look forward to really more exciting times reading here. Thanks a lot once again for a lot of things.

  19. Thanks so much for giving everyone an extraordinarily terrific opportunity to read articles and blog posts from this blog. It can be very ideal and as well , jam-packed with amusement for me and my office peers to visit your site at minimum 3 times weekly to study the fresh things you will have. And indeed, we’re at all times astounded considering the remarkable strategies you give. Some 4 ideas in this post are in truth the most impressive we have had.

  20. I truly wanted to send a simple message so as to thank you for these remarkable steps you are writing here. My considerable internet research has at the end been paid with professional strategies to talk about with my neighbours. I would suppose that many of us website visitors actually are definitely blessed to dwell in a wonderful site with many outstanding individuals with helpful tips and hints. I feel very grateful to have discovered your website and look forward to so many more fun moments reading here. Thanks a lot again for everything.

  21. Yay google is my queen helped me to find this great internet site!.

  22. Wonderful website. Plenty of helpful info here. I am sending it to a few buddies ans also sharing in delicious. And obviously, thank you on your sweat!

  23. Very neat article.Really looking forward to read more. Keep writing.

  24. I simply could not leave your site prior to suggesting that I really loved the standard info an individual supply to your guests? Is gonna be again regularly to investigate cross-check new posts.

  25. Really enjoyed this article post.Much thanks again. Great.

  26. A lot of thanks for your own effort on this blog. My mother delights in setting aside time for research and it is easy to understand why. We all notice all concerning the compelling mode you offer very helpful items through this blog and encourage response from visitors on that area then our own daughter is actually becoming educated a lot of things. Take advantage of the remaining portion of the new year. You’re the one performing a fabulous job.

  27. Major thankies for the post.Thanks Again. Keep writing.

  28. Hello! Someone in my Facebook group shared this site with
    us so I came to give it a look. I’m definitely enjoying the information. I’m book-marking and will be tweeting this to my followers!
    Superb blog and great design.

    magliette Olympique Marseille

  29. Very useful info аАааАТ‚artаАаб‚Т€Т“cularly the last part I

  30. A lot of thanks for each of your hard work on this web site. My daughter really loves engaging in investigations and it’s simple to grasp why. A number of us learn all about the compelling way you produce both interesting and useful guidance by means of your web site and as well improve response from the others about this article so our own simple princess is certainly studying a great deal. Take advantage of the rest of the new year. You have been conducting a terrific job.

  31. I would like to voice my affection for your kind-heartedness in support of people that require assistance with the study. Your real dedication to getting the message all-around turned out to be astonishingly advantageous and have continually permitted associates just like me to achieve their objectives. This helpful guideline indicates a lot to me and even more to my peers. Thanks a lot; from all of us.

  32. My spouse and i got quite fortunate when Albert managed to complete his analysis because of the precious recommendations he made out of the blog. It is now and again perplexing just to always be giving freely secrets and techniques which usually other people may have been selling. So we know we need the blog owner to be grateful to because of that. All the illustrations you made, the easy blog menu, the friendships you will aid to engender – it is most fantastic, and it is leading our son and us imagine that that matter is thrilling, which is certainly pretty essential. Thank you for the whole lot!

  33. You made some respectable points there. I seemed on the internet for the problem and located most individuals will associate with together with your website.

  34. I enjoy you because of all your hard work on this web site. Betty loves managing internet research and it is simple to grasp why. Many of us learn all regarding the lively means you render rewarding guidelines by means of your blog and increase contribution from other individuals about this subject plus our own princess has always been understanding a lot of things. Enjoy the remaining portion of the year. You are performing a fantastic job.

  35. I wish to point out my appreciation for your kindness in support of people who actually need help on in this theme. Your very own dedication to passing the solution all over became exceptionally advantageous and has specifically enabled guys like me to realize their targets. Your own important guideline means much a person like me and substantially more to my mates. With thanks; from all of us.

  36. wow, awesome post.Thanks Again. Really Cool.

  37. Really enjoyed this blog.Really looking forward to read more. Will read on

  38. I really liked your article.Much thanks again. Keep writing.

  39. I must show my appreciation to the writer just for bailing me out of this particular problem. Just after researching throughout the internet and getting tips which are not beneficial, I figured my entire life was gone. Existing without the answers to the issues you’ve solved through your entire blog post is a critical case, and those that could have in a wrong way affected my entire career if I hadn’t discovered your web blog. Your good mastery and kindness in handling every item was priceless. I am not sure what I would’ve done if I hadn’t come across such a solution like this. I can also at this time look ahead to my future. Thank you very much for the professional and sensible help. I will not think twice to refer the website to anyone who would like recommendations about this situation.

  40. Thanks for your whole effort on this web page. Kim loves going through investigation and it’s really simple to grasp why. A lot of people notice all of the powerful method you render useful steps through the web blog and as well as improve response from other individuals on that topic then our own daughter has always been understanding so much. Take pleasure in the rest of the year. You have been performing a remarkable job.

  41. I precisely desired to thank you so much again. I am not sure the things I might have achieved in the absence of those aspects documented by you over this concern. It actually was the intimidating matter in my circumstances, but being able to view a new specialised technique you processed it took me to leap for joy. Now i’m thankful for your support and as well , pray you know what an amazing job that you’re accomplishing training others with the aid of your web blog. More than likely you have never met all of us.

  42. omg! can at imagine how fast time pass, after August, ber months time already and Setempber is the first Christmas season in my place, I really love it!

Comments 101 - 142 of 142First« PrevNext »Last

Leave a Reply