RNA slippage used as approach to tackling HIV

Rhibosomes are the structures in cells which make proteins by reading the code of messenger RNA. The RNA appears on a frame and there can be slippage. If this happens, it can be used for some other productive purpose by the rhibosome. Warren Tate's lab is using this feature as the basis for an approach to tackling HIV in collaboration with the Walter and Eliza Hall Institute in Melbourne.
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This was an audio broadcast on Australian Broadcasting Corp.'s Radio National The Science Show, Saturday 31 March 2012 12:50PM
The Show's guest was researcher:
Warren Tate, Professor of Biochemistry, University of Otago, Dunedin, New Zealand
http://biochem.otago.ac.nz/professor-warren-tate/

http://www.jci.org/articles/view/61429?key=b299fdfbdc1c9633aa06

"Public release date: 16-Apr-2012

Replication of immunodeficiency virus in humans

VIROLOGY Replication of immunodeficiency virus in humans

The acquired immunodeficiency syndrome (AIDS) pandemic is caused by the human immunodeficiency virus (HIV-1), which attacks the immune system and leaves infected individuals susceptible to opportunistic infections. AIDS and HIV-1 are thought to have a relatively short history in humans, with the first infections likely occurring around the turn of the 20th century. HIV-1 is derived from highly related simian immunodeficiency viruses (SIVs) that infect modern primates, including chimpanzees. SIVs must have crossed the species barrier to infect humans at some point in the past, but the molecular adaptations that permitted a new host are unknown. Drs. Beatrice Hahn and Frank Kirchoff led an international research effort to understand what adaptations allow a chimpanzee strain of SIV to replicate in human tissues. They found that SIV is capable of replicating in human immune tissues, but that replication occurs at very low levels. By introducing a single amino acid change into the SIV Gag protein, a structural protein that makes up the viral capsid, the research team found that viral replication in cultured human tissues increased dramatically, while replication in chimpanzee-derived immune cells was decreased. Their work indicates that species-specific adaptation of Gag is critical for viral replication efficiency and suggests that changes in Gag potentially played a role in the emergence of HIV/AIDS..."

I have been reading anecdotal comments by others going back years, plus occasionally published African research that Neem might be capable of doing HIV significant damage, specially if taken in earlier phases of the infection, and could trigger substantial increases in CD4 counts. Very pleased to read that this potentially lower cost potential treatment source may be being investigated systematically. It may not be very profitable for big Pharmaceutical Companies to follow up on this however as there may not be outputs that they can easily patent. Looks like an excellent area for the World Community Grid FAAH project to provide assistance.

http://www.eurekalert.org/pub_releases/2012-04/asfb-sht041712.php

"Public release date: 22-Apr-2012

American Society for Biochemistry and Molecular Biology

Preliminary data hint at how extracts from the tree, abundant in tropical and subtropical areas, may stop the virus from multiplying

Tall, with dark-green pointy leaves, the neem tree of India is known as the "village pharmacy." As a child growing up in metropolitan New Delhi, Sonia Arora recalls on visits to rural areas seeing villagers using neem bark to clean their teeth. Arora's childhood memories have developed into a scientific fascination with natural products and their power to cure illnesses.

Now an assistant professor at Kean University in New Jersey, Arora is delving into understanding the curative properties of the neem tree in fighting the virus that causes AIDS. She will be presenting her data at a poster session at 12:25 p.m. Sunday, April 22, at the Experimental Biology 2012 meeting in San Diego. Her preliminary results seem to indicate that there are compounds in neem extracts that target a protein essential for HIV to replicate. If further studies support her findings, Arora's work may give clinicians and drug developers a new HIV-AIDS therapy to pursue.

Extracts from neem leaves, bark and flowers are used throughout the Indian subcontinent to fight against pathogenic bacteria and fungi. "The farther you go into the villages of India, the more uses of neem you see," says Arora. Tree branches are used instead of toothpaste and toothbrushes to keep teeth and gums healthy, and neem extracts are used to control the spread of malaria.

Practitioners of Ayurvedic medicine, a form of traditional Indian alternative medicine, even prescribe neem extracts, in combination with other herbs, to treat cardiovascular diseases and control diabetes. The neem tree, whose species name is Azadirachta indica and which belongs to the mahogany family, also grows in east Africa.

Arora's scientific training gave her expertise in the cellular biology of cancer, pharmacology, bioinformatics and structural biology. When she established her laboratory with a new research direction at Kean University in 2008, Arora decided to combine her knowledge with her long-time fascination with natural products. The neem tree beckoned.

Arora dived into the scientific literature to see what was known about neem extracts. During the course of her reading, Arora stumbled across two reports that showed that when HIV-AIDS patients in Nigeria and India were given neem extracts, the amount of HIV particles in their blood dropped. Intrigued, Arora decided to see if she could figure out what was in the neem extract that seemed to fight off the virus.

She turned to bioinformatics and structural biology to see what insights could be gleaned from making computer models of HIV proteins with compounds known to be in neem extracts. From the literature, she and her students found 20 compounds present in various types of neem extracts. When they modeled these compounds against the proteins critical for the HIV life-cycle, Arora and her team discovered that most of the neem compounds attacked the HIV protease, a protein essential for making new copies of the virus.

Arora's group is now working on test-tube experiments to see if the computer models hold up with actual samples. If her work bears out, Arora is hopeful that the neem tree will give a cheaper and more accessible way to fight the HIV-AIDS epidemic in developing countries, where current therapies are priced at levels out of reach of many people. "And, of course," she notes, "there is the potential of discovering new drugs based on the molecules present in neem."

http://www.medicalnewstoday.com/articles/244721.php

"Article Date: 27 Apr 2012 - 14:00 PDT

FDA Update Safety Information On HIV Drug Victrelis (Boceprevir)

The United States Food and Drug Administration (FDA) is updating information on Victrelis (boceprevir). The drug is used as a hepatitis C (HCV) protease inhibitor. It is combined with various ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors.

The FDA is stating that it cannot recommend use of the drug at this time, because it appears to reduce effectiveness of other medications and has been seen to cause HCV and HIV to increase in the bloodstream. This is known as the viral load, and obviously leads to the diseases becoming more potent and aggressive.

Ritonavir-boosted HIV protease inhibitors include ritonavir-boosted Reyataz (atazanavir), ritonavir-boosted Prezista (darunavir), and Kaletra (lopinavir/ritonavir). Ritonavir is an HIV protease inhibitor that is taken as a small dose along with other HIV protease inhibitors in order to increase their levels in the blood and make them more effective. This is known as ritonavir boosting.

The FDA states that patients should not simply stop taking their medicines on FDA advice, but must seek consultation with their physician as to the best course of action for their particular situation.

The FDA also issues advice for healthcare professionals who are treating patients with chronic HCV and HIV, using Victrelis where the patient was taking antiretroviral therapy in the form of ritonavir-boosted protease inhibitors. The patient's response to the drug combination should be closely monitored for any unexpected increase in virus levels..."

http://www.medicalnewstoday.com/releases/238120.php

"Article Date: 25 Nov 2011

The Burden Of Cancer In Those With HIV May Be Alleviated By Earlier Antiretroviral Therapy

HIV-infected patients are at increased risk for cancer as a result of both their impaired immune system and lifestyle factors, such as smoking, according to researchers at Kaiser Permanente.

The study, which appears in the current issue of Cancer Epidemiology, Biomarkers and Prevention, is among the first to directly compare the risk of cancer in HIV-infected patients with a comparison group without HIV infection, while accounting for major cancer risk factors..."