http://www.medicalnewstoday.com/releases/270201.php

Wednesday 18 December 2013

"Cardiovascular risk in HIV-infected women likely related to plaque composition, immune activation

A Massachusetts General Hospital (MGH) research team has discovered a possible mechanism behind the elevated risk of cardiovascular disease in women infected with HIV, a risk even higher than that of HIV-infected men. In the Journal of Infectious Diseases the investigators report finding that HIV-infected women had a greater prevalence of the type of coronary artery plaque most vulnerable to rupture than did uninfected women. They also found evidence that increased immune system activation may contribute to development of vulnerable plaques, an association that appears to be further amplified in older women.

"Studies have found rates of heart attack and stroke in HIV-infected patients that are from 50 to 100 percent higher than those of uninfected individuals, with particularly high rates - almost tripled in some studies - in women," says Steven Grinspoon, MD, director of the MGH Program in Nutritional Metabolism and a member of the Neuroendocrine Unit, the study's principal investigator. "Traditional cardiovascular risk factors only account for part of the excess risk, and previous studies from our group have found both increased immune activation and high-risk vulnerable plaque in HIV-infected men, but this is the first to assess these factors in HIV-infected women."

http://www.medicalnewstoday.com/releases/270457.php

Saturday 28 December 2013

"Advances in HIV vaccine research likely following animal vaccine study

A vaccine study in monkeys designed to identify measurable signs that the animals were protected from infection by SIV, the monkey version of HIV, as well as the mechanism of such protection has yielded numerous insights that may advance HIV vaccine research. Seven laboratories collaborated on the research led by Mario Roederer, Ph.D., and John R. Mascola, M.D., at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

By examining both viral amino-acid sequences and the animals' immune responses, the scientists could determine the mechanisms of protection from SIV infection. The study demonstrated that antibodies to the virus spikes that SIV uses to infect cells are necessary and sufficient to prevent SIV infection. The study also identified clear measures of immune responses in monkeys that predict protection from SIV infection......"

http://www.medicalnewstoday.com/releases/272849.php

Thursday 20 February 2014

"For the more than one million people with HIV/AIDS in the United States (and the over 34 million people living with HIV/AIDS around the world), antiretroviral drugs such as efavirenz and other so-called non-nucleoside reverse transcriptase inhibitors (NNRTIs) in combination with other antiretrovirals can be a lifeline, because they slow the progress of viral infection, prolonging life. Unfortunately, studies have shown that these benefits themselves can be short-lived in the clinic: therapy with NNRTIs can lead to single (or "point") mutations in the HIV genetic code -- mutations that make the virus resistant to the drugs.

Researchers at the University of Pittsburgh School of Medicine now have a good idea why. In work presented at the 58th Annual Biophysical Society Meeting, which took place in San Francisco from Feb. 15-19, cell biologist Sanford Leuba and his colleagues offer new insight into how NNRTIs function and how therapy-induced point mutations actually confer drug resistance.

NNRTIs work by blocking the action of an enzyme called reverse transcriptase, which HIV uses to convert its own genetic material (in the form of RNA) into single-stranded copies of DNA, which can then be inserted into the genome of the human cells they've infected. Once incorporated, this DNA instructs the host to create new copies of the virus, propagating the infection to new cells and over time attacking the immune system, which can lead to full-blown AIDS.

Using a number of imaging techniques and computer modeling, Leuba and his team showed that, normally, the binding of efavirenz results in the formation of a molecule-sized "salt bridge" that holds the reverse transcriptase in an open state when it is attached to the template it uses in making DNA copies. "The reverse transcriptase can still bind the template, but it continually slides," Leuba explained, "preventing the enzyme from polymerizing nucleotides. The virus cannot replicate."

The point mutations that cause resistance to efavirenz, the researchers found, prevent that salt bridge from forming, "allowing the reverse transcriptase to function normally," he says. "This type of inhibition, which does not involve drug-binding affinity, has not been described previously."

Based on the work, Leuba said, "We have ideas about how to begin designing a new generation of NNRTIs."

http://www.medicalnewstoday.com/releases/273228.php

Thursday 27 February 2014

"Byproducts from bacteria-causing gum disease incite deadly oral cancer growth

Researchers from Case Western Reserve University have discovered how byproducts in the form of small fatty acids from two bacteria prevalent in gum disease incite the growth of deadly Kaposi's sarcoma-related (KS) lesions and tumors in the mouth.

The discovery could lead to early saliva testing for the bacteria, which, if found, could be treated and monitored for signs of cancer and before it develops into a malignancy, researchers say.

"These new findings provide one of the first looks at how the periodontal bacteria create a unique microenvironment in the oral cavity that contributes to the replication the Kaposi's sarcoma Herpesvirus (KSHV) and development of KS," said Fengchun Ye, the study's lead investigator from Case Western Reserve School of Dental Medicine's Department of Biological Sciences.

The discovery is described in The Journal of Virology article, "Short Chain Fatty Acids from Periodontal Pathogens Suppress HDACs, EZH2, and SUV39H1 to Promote Kaposi's Sarcoma-Associated Herpesvirus Replication."

The research focuses on how the bacteria, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn), which are associated with gum disease, contribute to cancer formation.

Ye said high levels of these bacteria are found in the saliva of people with periodontal disease, and at lower levels in those with good oral health - further evidence of the link between oral and overall physical health.

KS impacts a significant number of people with HIV, whose immune systems lack the ability to fight off the herpesvirus and other infections, he said.

"These individual are susceptible to the cancer," Ye said.

KS first appears as lesions on the surface of the mouth that, if not removed, can grow into malignant tumors. Survival rates are higher when detected and treated early in the lesion state than when a malignancy develops.

Also at risk are people with compromised immune systems: people on medications to suppress rejection of transplants, cancer patients on chemotherapies and the elderly population whose immune systems naturally weaken with age.

The researchers wanted to learn why most people never develop this form of cancer and what it is that protects them.

The researchers recruited 21 patients, dividing them into two groups. All participants were given standard gum-disease tests.

The first group of 11 participants had an average age of 50 and had severe chronic gum disease. The second group of 10 participants, whose average age was about 26, had healthy gums, practiced good oral health and showed no signs of bleeding or tooth loss from periodontal disease.

The researchers also studied a saliva sample from each. Part of the saliva sample was separated into its components using a spinning centrifuge. The remaining saliva was used for DNA testing to track and identify bacteria present, and at what levels.

The researchers were interested in Pg's and Fn's byproducts of lipopolysaccharide, fimbriae, proteinases and at least five different short-chain fatty acids (SCFA): butyric acid, isobutryic acid, isovaleric acid, propionic acid and acetic acid.

After initially testing the byproducts, the researchers suspected that the fatty acids were involved in replicating KSHV. The researchers cleansed the fatty acids and then introduced them to cells with quiescent KSHV virus in a petri dish for monitoring the virus' reaction.

After introducing SCFA, the virus began to replicate. But the researchers saw that, while the fatty acids allowed the virus to multiple, the process also set in motion a cascade of actions that also inhibited molecules in the body's immune system from stopping the growth of KSHV.

"The most important thing to come out of this study is that we believe periodontal disease is a risk factor for Kaposi sarcoma tumor in HIV patients," Ye said.

With that knowledge, Ye said those with HIV must be informed about the importance of good oral health and the possible consequences of overlooking that area."

Earliest possible treatment does not stop forming any 'untouchable' viral reservoirs. http://www.bbc.com/news/health-28352370

Brief excerpt