ScienceDaily (Nov. 17, 2007) — Natural HIV-1 infection does not always elicit a protective immune response, according to a new study.

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A team of researchers from Washington University, the Fred Hutchinson Cancer Research Center of Seattle, and the University of Nairobi show how HIV-1 vaccines may not be as reliable against superinfection as once thought.

Superinfection of HIV-1 occurs when an individual infected with one strain of HIV-1 acquires a second strain. Currently there are over 20 published cases of HIV-1 superinfection, most of which have been focused on individuals who have been carefully monitored during their infection. These cases prove that an HIV-1 vaccine may not always protect against infection by a different strain. But because there have been reports of selected individuals, it has been unclear how commonly HIV-1 re-infection occurs.

To address this question, Dr. Julie Overbaugh and her research team investigated the incidence of HIV-1 superinfection in 36 high-risk women followed roughly five years after their initial infection.

Seven cases of superinfection were found; five of them occurring over a year past initial infection. Additionally, three of the seven cases displayed a virus from the same HIV-1 genetic subtype.

This study suggests that immune responses found in natural HIV-1 infection, which fail to provide protection against re-infection, may not be the best path to an effective HIV-1 vaccine.

Journal article: Piantadosi A, Chohan B, Chohan V, McClelland RS, Overbaugh J (2007) Chronic HIV-1 infection frequently fails to protect against superinfection. PLoS Pathog 3(11):e177. doi:10.1371/journal.ppat.0030177

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Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

ScienceDaily (Apr. 25, 2008) — Just as fire engines arrive quickly at the scene to save people and property, the cells that fight viruses have to reach the site of an infection promptly to mount a protective response.

According to recent studies by University of Washington (UW) scientists, specialized types of white blood cells, a category called regulatory T cells, seem to help orchestrate this timely reaction to a virus invasion.

The Rudensky laboratory is noted for many contributions to the superhot field of regulatory T cells. These cells are important in controlling autoimmunity, a cellular self-attack that can lead to diseases like reactive arthritis. UW researchers and other scientists have shown that young mice deficient in regulatory T cells die from an aggressive form of autoimmunity that damages several organs.

Alexander Y. Rudensky, professor of immunology, noted the great clinical interest in the therapeutic potential of regulatory T cells. Evidence is growing on the role of regulatory T cells in keeping the body’s immune responses in check. Studies in lab animals suggest these cells might be harnessed to treat autoimmune diseases or reduce rejection of transplanted organs.

Researchers think that regulatory T cells might call a halt to immune responses as the body nears success in eliminating an infection. This suppression as the fight draws to an end would reduce tissue damage from robust immune responses.

But what happens early in infection? Does the immunity-suppressing function of regulatory T cells form an obstacle to organizing an attack on germs that have just invaded the body? Do regulatory T cells temporarily lose their suppression ability in reaction to viral-sensing mechanisms or other signals? In the recent Science Express study, researchers looked for a role for regulatory T cells during the start of a herpes simplex virus infection in mucus membranes.

When regulatory T cells are deficient in mice, the herpes simplex virus replicates rapidly in the mucus membranes and spreads to the spinal cord. Upon closer examination of these mice that lack regulatory T cells, the researchers found very little interferon, an anti-viral chemical that also boosts the immune response, at the infection site, even though it was found in the draining lymph nodes.

Also in the lymph nodes they noticed a sharp increase in certain chemokines, chemicals that stimulate immune cells to move in and cause inflammation. The presence of chemokines appeared to encourage the entry and retention of certain infection-fighting cells in the lymph nodes draining the site of infection, an ineffective place for the infection-fighting cells to be during the start of a viral attack.

The researchers also noticed a delay in killer cells, dendritic cells (the cells that capture and present foreign proteins to other immune cells), and T cells arriving at the site of infection, where they were supposed to go earlier to fulfill their virus-fighting roles. The researchers suggested that a possible reason for this tardiness is an alteration in the chemical cues necessary for these cells to migrate to the site of infection.

The authors described the finding of an immune-response promoting role for regulatory T cells during the early stages of a local infection as “unexpected,” considering the cells’ suppressor roles during later stages of an immune response.

Findings appear in the April 24 edition of Science Express. The authors of the study, “Coordination of Early Protective Immunity to Viral Infections by Regulatory T Cells,” are Jennifer M. Lund, senior fellow in immunology; Lianne Hsing, immunology graduate student; Thuy T. Pham, senior biology major; and Alexander Y. Rudensky, professor of immunology.

Adapted from materials provided by University of Washington, via EurekAlert!, a service

University of Washington (2008, April 25). Specialized White Blood Cells Coordinate First Responders To Viral Infection. ScienceDaily. Retrieved April 25, 2008, from http://www.sciencedaily.com­ /releases/2008/04/080424152249.htm

Damage to the lining of the mouth and a weakened immune system make it easier for infection to occur.

Oral mucositis breaks down the lining of the mouth, allowing germs and viruses to get into the bloodstream. When the immune system is weakened by chemotherapy, even good bacteria in the mouth can cause infections, as can disease-causing organisms picked up from the hospital or other sources. As the white blood cell count gets lower, infections may occur more often and become more serious. Patients who have low white blood cell counts for a long time are more at risk of developing serious infections. Dry mouth, common during radiation therapy to the head and neck, may also raise the risk of infections in the mouth. Preventive dental care during chemotherapy and radiation therapy can reduce the risk of mouth, tooth, and gum infections.

The following types of infections may occur:

Bacterial infections

Treatment of bacterial infections in patients who have gum disease and receive high-dose chemotherapy may include the following:

• Medicated and peroxide mouth rinses.
• Brushing and flossing.
• Wearing dentures as little as possible.

Bacterial infections in patients undergoing radiation therapy are usually treated with antibiotics.

Fungal infections

The mouth normally contains fungi that can exist on or in the body without causing any problems. An overgrowth of fungi, however, can be serious and requires treatment.

Antibiotics and steroid drugs are often used when a patient receiving chemotherapy has a low white blood cell count. These drugs change the balance of bacteria in the mouth, making it easier for a fungal overgrowth to occur. Fungal infections are common in patients treated with radiation therapy.

Drugs may be given to prevent fungal infections from occurring. Treatment of surface fungal infections in the mouth only may include mouthwashes and lozenges that contain antifungal drugs. These are used after removing dentures, brushing the teeth, and cleaning the mouth. An antibacterial rinse should be used on dentures and dental appliances and to rinse the mouth.

Deeper fungal infections, such as those in the esophagus or intestines, are treated with drugs taken by mouth or injection.

Viral infections

Patients receiving chemotherapy, especially those with weakened immune systems, are at risk of mild to serious viral infections. Finding and treating the infections early is important. Drugs may be used to prevent or treat viral infections.

Herpes virus infections may recur in radiation therapy patients who have these infections.

Bleeding

Bleeding may occur during chemotherapy when anticancer drugs affect the ability of blood to clot.

Areas of gum disease may bleed on their own or when irritated by eating, brushing, or flossing. Bleeding may be mild (small red spots on the lips, soft palate, or bottom of the mouth) or severe, especially at the gumline and from ulcers in the mouth. When blood counts drop below certain levels, blood may ooze from the gums.

With close monitoring, most patients can safely brush and floss throughout the entire time of decreased blood counts.

Continuing regular oral care will help prevent infections that may further complicate bleeding problems. The dentist or doctor can provide guidance on how to treat bleeding and safely keep the mouth clean when blood counts are low.

Treatment for bleeding during chemotherapy may include the following:

• Medications to reduce blood flow and help clots form.
• Topical products that cover and seal bleeding areas.
• Rinsing with a mixture of one part 3% hydrogen peroxide to 2 or 3 parts saltwater solution (1 teaspoon of salt in 4 cups of water) to help clean oral wounds. Rinsing must be done carefully so clots are not disturbed.