Links In Fluids to HIV Viral Load and Transmission

While HIV is found in many body fluids, sexual transmission through semen is the most common route of infection. Consequently, the amount of virus in semen (the semen viral load) affects the likelihood of HIV transmission. Besides sperm, semen also contains immune factors and communities of bacteria, an environment that could influence the viral load. Research published recently in PLOS Pathogens reports that HIV infection re-shapes the relationship between semen bacteria and immune factors which in turn affects viral load, suggesting that the semen microbiome plays a role in sexual transmission of HIV.

Researchers led by Lance Price, from the Translational Genomics Research Institute, USA, and Rupert Kaul, from the University of Toronto, Canada, studied the relationship of semen bacteria with HIV infection by analyzing semen samples from 49 men who have sex with men (MSM). They focused on MSM because of the high risk of sexual HIV transmission in this population. 27 of the men were HIV infected, and provided samples both before they started anti-retroviral therapy (ART) and one and six months after. Samples from 22 MSM not infected with HIV served as controls.

University of Toronto

In HIV-infected men not on ART, overall numbers of bacteria in the samples—the semen bacterial load—was correlated with HIV viral load. Analyzing the bacterial DNA in the samples, the researchers detected a total of 248 unique types of bacteria in semen from the controls, on average 71 different ones per sample. In samples from HIV-infected untreated men, semen microbiome diversity was markedly reduced, and the relative abundance of the more common bacterial groups differed. ART for six months reduced semen viral load to undetectable levels, and restored bacterial diversity and composition to a situation similar to the controls.

There was no correlation in uninfected controls between levels of immune factors and semen bacterial load. In contrast, in HIV-infected men, several factors, and most strongly one called interleukin-1beta (IL-1b), a mediator of inflammation, showed a correlation with both semen bacterial load and semen viral load.

“While delineating the directionality and causality of the complex relationships they observed will require further studies”, the researchers say, their data “suggest an interaction between semen microbiome, local immunology, and semen viral load. Higher bacterial load in semen could lead to higher IL-1b levels, which in turn could induce viral shedding, thereby increasing viral load.” They conclude that the results “support the hypothesis that semen bacteria play a role in local inflammation and HIV shedding, and that they are a possible target for reducing HIV transmission.”

- MFP News Services
- 11/19/14

Pesticide Connected to Three Generations of Disease

PULLMAN, Washington. – Washington State University researchers say ancestral exposures to the pesticide methoxychlor may lead to adult onset kidney disease, ovarian disease and obesity in future generations.

Washington State University

“What your great-grandmother was exposed to during pregnancy, like the pesticide methoxychlor, may promote a dramatic increase in your susceptibility to develop disease, and you will pass this on to your grandchildren in the absence of any continued exposures,” says Michael Skinner, WSU professor and founder of its Center for Reproductive Biology.

He and his colleagues document their findings in a paper published online in PLOS ONE. The study was funded by the National Institutes of Health.

Methoxychlor—also known as Chemform, Methoxo, Metox or Moxie—was introduced in 1948 and widely used during the 1970s as a safer replacement for DDT. It was used on crops, ornamental plants, livestock and pets. It is still used in many countries around the world.

It was banned in the U.S. in 2003 due to its toxicity and ability to disrupt endocrine systems. Methoxychlor can behave like the hormone estrogen and profoundly affects the reproductive system.

Supports earlier epigenetic findings

When Skinner and his colleagues exposed gestating rats to methoxychlor at a range typical of high environmental exposures, they saw increases in the incidence of kidney disease, ovary disease and obesity in offspring spanning three generations. The incidence of multiple diseases increased in the third generation or “great-grandchildren.”

The researchers say the pesticide may be affecting how genes are turned on and off in the progeny of an exposed animal, even though its DNA and gene sequences remain unchanged.

This is called transgenerational epigenetic inheritance. In recent years, the Skinner lab has documented epigenetic effects from a host of environmental toxicants, including DDT, plastics, pesticides, fungicides, dioxins, hydrocarbons and the plasticizer bisphenol-A or BPA. The newest findings support those observations.

Implications for obesity, fertility, disease

The work is also the first to show that a majority of transgenerational disease traits can be transmitted primarily through the female line.

Additionally, the study identified mutations in the sperm epigenome of great-grandchild male rats. The epigenome functions like a set of switches for regulating gene expression and can be altered by environmental conditions.

The epigenetic changes observed were specific to methoxychlor exposure and may prove to be valuable biomarkers for future research on transgenerational disease.

For people exposed to the pesticide, Skinner says his findings have implications such as reduced fertility, increased adult onset disease and the potential to pass on those conditions to subsequent generations.

He suggests that ancestral exposures to methoxychlor over the past 50 years in North America may play a part in today’s increasing rates of obesity and disease.

- MFP News Services
- 11/18/14

Autoimmune Disorders Could Share Pathogenic Mechanisms with Cancer

Autoimmune disorders may share certain pathogenic mechanisms with cancer, according to a new report by George Washington University (GW) researcher Linda Kusner, Ph.D., published in PLOS ONE recently.

George Washington University Medical Center

This paradigm shifting work shows that the very same inhibitors of apoptosis, or cell destruction, in tumors are also expressed in cells that produce autoimmune diseases. Henry Kaminski, M.D., chair of the Department of Neurology at the GW School of Medicine and Health Sciences (SMHS), as well as colleagues from the Roswell Park Cancer Institute, collaborated with Kusner’s laboratory on this research. Together they discovered that survivin, an inhibitor of apoptosis, is also expressed in the white blood cells, called lymphocytes, of patients with the autoimmune disease myasthenia gravis, but not in normal individuals. This was also the case in animal models of myasthenia gravis. Myasthenia gravis is a severe muscle disease that can lead to such weakness that patients must be placed on breathing machines.

“We found that humans with myasthenia gravis also express survivin in autoreactive lymphocytes,” said Kusner, assistant research professor in the Department of Pharmacology and Physiology at SMHS. “We found these cells to be part of the dysfunction underlying the autoimmune disease.”

Using a vaccine technique, the research team was able to eliminate the survivin-expressing cells and demonstrate improvement in the animal models with myasthenia gravis. Kusner’s laboratory will continue to work to improve the inhibition of survivin as a treatment and one day bring survivin targeted treatment to patients.

“This study opens a new therapeutic approach for myasthenia gravis, as well as other autoimmune disorders,” said Kaminski. “Conventional therapies may improve the disease, but have numerous complications. This discovery may lead to a viable treatment option for the millions of American suffering from these disorders.”

- MFP News Services
- 11/11/14