Washington, March 18: A team of researchers involving an Indian origin boffin has solved the mystery of how stealthy HIV protein gets into cells.

Boffins have known for quite some time that a protein called TAT is good at crossing cell membranes. However, how exactly it worked has been of much curiosity.

TAT is not involved in transmitting the HIV virus; it only aids the passage of other materials across the membranes of infected cells.

Now, a multidisciplinary team from the University of Illinois involving graduate student Abhijit Mishra, materials science and engineering professor Gerard Wong; and postdoctoral researcher Vernita Gordon, has solved this mystery, something that could help improve the design of therapeutic agents that cross a variety of membrane types.

Lead author of the study Gerard Wong said, "TAT is extremely good at getting through cell membranes. You can attach TAT to almost anything and it will drag it across the membrane. It can work for virtually all tissues, including the brain."

The TAT protein transduction domain of the HIV virus is a tiny part of the overall TAT protein, containing only 11 amino acids, of which six are arginine, a positively charged amino acid that gives the protein its activity.

Most membranes are composed of a double layer of neutral, water-repellent lipids on their interiors, with hydrophilic (water-loving) "head groups" on their internal and external surfaces. The head groups generally carry a mildly negative charge.

Keeping these two things in mind, the researchers had thought that any positively charged amino acid could deform the membrane in a way that opened up a pathway through it.

However, when they replaced the arginine in the protein with other positively charged amino acids, it lost its function.

Using confocal microscopy and synchrotron x-ray scattering (SAXS), where the pattern of X-ray scattering can reveal how atomic and nano scale materials are structured, researchers found that adding the TAT protein to a membrane completely altered its SAXS spectrum, a sign that the membrane conformation had changed.

Upon analyzing the spectrum, they noted that TAT had completely reconstructed the membranes and made them porous thus making it easier for other biological processes to bring materials through.

Further analysis showed that the arginine was interacting with the head groups on the membrane lipids in a way that caused the membrane to buckle in two different directions, bringing on the saddle splay curvature that allowed the pores to form.

When another positively charged amino acid, lysine, was used instead of arginine, the protein bent the membrane in one direction only, forming a shape more like a closed cylinder that would not allow materials to pass through.

These findings will aid researchers hoping to enhance the properties of the TAT protein that make it a good vehicle for transporting therapeutic molecules into cells.

The paper describing the findings appears this month in Angewandte Chemie.

Washington, February 8: Researchers at the University of Washington and the University of Rochester Medical Center, have found that "good bacteria" or beneficial bacteria found in healthy women may help in reducing the amount of vaginal HIV among HIV-infected women and may also make it difficult for the virus to spread.

The findings may bolster the possibility that these "good bacteria", which are the Lactobacillus bacteria in the vagina, might one day be useful in combating HIV.

The study led by Jane Hitti, M.D., associate professor in the Department of Obstetrics and Gynecology at the University Of Washington School Of Medicine, involved 57 women and was done in Seattle and Rochester through the Women's HIV Interdisciplinary Network (WHIN), based at the University of Washington.

The researchers studied the vaginal bacteria to look at the mix of bacteria that reside there and took many other factors in consideration. They tracked the level of HIV virus in the vagina, infection by common sexually transmitted diseases like trichomoniasis, gonorrhea and chlamydia, and other more common types of vaginal infections.

The researchers also examined the levels of Lactobacillus in the vagina, and also the hydrogen peroxide, which is produced by the bacteria and hinders the virus. The level on HIV in the women's blood and the rate of progression of the disease overall was also measured.It was discovered that women with hydrogen-peroxide-producing Lactobacillus in the vagina had lower levels of HIV virus in genital secretions, called the genital viral load in physicians' jargon. It is known that with lower level of HIV in the sexual tract, the virus will be less likely to spread from person to person through sexual contact.

In earlier studies, Lactobacillus was found to give women some natural protection against HIV. These bacteria, commonly found in most women, bind to the virus and secrete hydrogen peroxide.

While previous studies also mentioned that Lactobacillus might be useful in preventing HIV infection in women, the current study establishes a link between decreased levels of the virus in the vagina with the presence of Lactobacillus that produce hydrogen peroxide there.

The researchers also discovered that the amount of the virus in the vagina changed with the presence of Lactobacillus. It was found that vaginal HIV levels drop in women who did not have the bacteria initially but had acquired it by a subsequent visit. On the other hand, vaginal HIV levels increased in women in whom the good bacteria had disappeared between visits.

"These findings underscore the importance of maintaining a healthy, Lactobacillus-dominant vaginal flora for HIV-positive women. I hope that we can explore Lactobacillus replacement in the future for women who do not have this bacteria, as a strategy to decrease the amount of HIV in the vagina," said Hitti.

The research was presented at the Conference on Retroviruses and Opportunistic Infections in Boston.

Researchers in Germany have discovered that a protein found in semen makes HIV 100,000 times more virulent than it is alone - thus helping to explain why more than 80 per cent of human-immunodeficiency-virus (HIV) infections are transmitted via sexual intercourse.

The team of German scientists had initially set out to determine whether semen contained factors that inhibit the HIV infection, according to the report published in the journal Cell.

But surprisingly, the HIV/AIDS researchers in Hanover and Ulm, Germany, found that fragments of prostatic acidic phosphatase isolated from human semen form tiny fibres known as amyloid fibrils, which they call Semen-derived Enhancer of Virus Infection or SEVI.

Those fibrils capture HIV particles and help them to penetrate target cells, thereby increasing the infection rate by up to several orders of magnitude.

"We were not expecting to find an enhancer, and we were even more surprised about the strength," says report co-author Frank Kirchhoff, a virologist at the University of Ulm Clinic in Germany.

"Most enhancers have maybe a two or three-fold effect, but here the effect was amazing. More than 50-fold and, under certain conditions, more than 100,000-fold," Kirchhoff says.

Wolf-Georg Forssmann of VIRO PharmaCeuticals GmbH & Co KG and Hanover Medical School says the fibrils act like a ferry, picking up the viruses and then bringing them to the cell.

Researchers injected both the naked virus and SEVI-treated HIV into the tails of rats that had been given human immune system cells.

The HIV with the semen component was five times more effective at transmitting the virus.

In situations where low levels of the virus are transferred - as during intercourse - Kirchhoff says, SEVI can make HIV up to 100,000 times more likely to spread when compared with the virus alone.

In an editorial accompanying the article, postdoctoral fellow Nadia Roan, along with Warner Greene, a senior investigator at the University of California, San Francisco's Gladstone Institute of Virology and Immunology, writes:

"If SEVI truly increases the real-world heterosexual spread of HIV by several orders of magnitude, then negating the activity of this factor could conceivably diminish these frequencies to levels that might virtually eliminate semen-driven HIV transmission."

HIV, the virus that leads to AIDS, has infected 60 million people worldwide (causing 25 million deaths) since it was discovered in humans in 1981.

The transmission rate from intravaginal sexual intercourse is estimated at one in every 200 to 2,000 acts. In Africa, 60 percent of new infections are in women who have had sex with HIV-positive men.