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MicroRNAs may be key to HIV's ability to hide, evade drugs, Jefferson scientists find
October 01, 2007(PHILADELPHIA) Tiny pieces of genetic material called microRNA (miRNA), better known for its roles in cancer, could be a key to unlocking the secrets of how HIV, the AIDS virus, evades detection, hiding in the immune system. Researchers at Jefferson Medical College in Philadelphia have shown that when an individual infected with HIV receives a powerful cocktail of antiviral agents called HAART (highly active antiretroviral therapy), the virus calls on miRNAs to help it remain quiet and practically undetectable, temporarily shutting down its ability to replicate and infect.
The work, which appears September 30, 2007 in an early online edition of the journal Nature Medicine, may also have implications for new treatment strategies against the virus. According to Hui Zhang, M.D., Ph.D., associate professor of Medicine in the Division of Infectious Diseases at Jefferson Medical College of Thomas Jefferson University, who led the work, if researchers can learn to manipulate miRNA's inhibitory effect on HIV, they might be able to devise strategies to bring the virus out of hiding, or "latency," making it vulnerable to drugs and the body's immune system.
While HAART can drive the number of HIV particles in the blood to practically undetectable levels, the virus is not eliminated. It hides in "resting" immune system CD4 T cells in the body, including the testis, brain, and other places. The drug combination has to be taken the rest of the patient's life; if halted, the virus becomes active again.
"HIV latency and how to eliminate the replication-competent - and hidden - virus are big problems," Dr. Zhang explains, noting that the molecular mechanisms that are responsible for latency are unclear.
Dr. Zhang, post-doctoral fellow Jialing Huang, Ph.D., and their colleagues may have come across one possible explanation. HIV, they have found, recruits cellular miRNA - noncoding genetic material that has been shown to play a variety of roles in cancer and in biological regulation - in resting T cells to "control the translation of viral RNA into protein." This is the last step in the creation of HIV antigens, which make the virus visible to the immune system.
The team showed that a cluster of miRNAs bind to a certain location on the viral RNA, which in turn, blocks the creation of important proteins, and HIV replication. Resting CD4 T cells, they found, are "enriched" with more than the normal amount of these miRNAs compared to the activated T cells. When the researchers used antisense technology to block miRNA-caused viral inhibition, they found that the HIV again was active and able to replicate - proving miRNA's critical role in maintaining latency.
While Dr. Zhang and his team continue to study how cellular miRNA contributes to latency, he notes that using miRNA inhibitors "might become a kind of therapeutic approach to get the virus out of hiding, making it visible and a target" for the immune system. "That's the next step," he says.
Thomas Jefferson University
"HIV latency and how to eliminate the replication-competent - and hidden - virus are big problems," Dr. Zhang explains, noting that the molecular mechanisms that are responsible for latency are unclear.
Dr. Zhang, post-doctoral fellow Jialing Huang, Ph.D., and their colleagues may have come across one possible explanation. HIV, they have found, recruits cellular miRNA - noncoding genetic material that has been shown to play a variety of roles in cancer and in biological regulation - in resting T cells to "control the translation of viral RNA into protein." This is the last step in the creation of HIV antigens, which make the virus visible to the immune system.
The team showed that a cluster of miRNAs bind to a certain location on the viral RNA, which in turn, blocks the creation of important proteins, and HIV replication. Resting CD4 T cells, they found, are "enriched" with more than the normal amount of these miRNAs compared to the activated T cells. When the researchers used antisense technology to block miRNA-caused viral inhibition, they found that the HIV again was active and able to replicate - proving miRNA's critical role in maintaining latency.
While Dr. Zhang and his team continue to study how cellular miRNA contributes to latency, he notes that using miRNA inhibitors "might become a kind of therapeutic approach to get the virus out of hiding, making it visible and a target" for the immune system. "That's the next step," he says.
Thomas Jefferson University
Immune System Current Events and Immune System News RSSSurface bacteria maintain skin's healthy balance
On the skin's surface, bacteria are abundant, diverse and constant, but inflammation is undesirable. Research at the University of California, San Diego School of Medicine now shows that the normal bacteria living on the skin surface trigger a pathway that prevents excessive inflammation after injury.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
Measuring and modeling blood flow in malaria
When people have malaria, they are infected with Plasmodium parasites, which enter the body from the saliva of a mosquito, infect cells in the liver, and then spread to red blood cells.
New cancer target for non-Hodgkin's lymphoma
Physician-scientists from Weill Cornell Medical College have discovered a molecular mechanism that may prove to be a powerful target for the treatment of non-Hodgkin's lymphoma, a type of cancer that affects lymphocytes, or white blood cells.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
New findings suggest strategy to help generate HIV-neutralizing antibodies
New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
UAB Researchers Discover Antibody Receptor Identity, Propose Renaming Immune-System Gene
Researchers at the University of Alabama at Birmingham (UAB) have uncovered the genetic identity of a cellular receptor for the immune system's first-response antibody, a discovery that sheds new light on infection control and immune disorders.
New culprit for viral infections among elderly -- an overactive immune response
Researchers at Yale School of Medicine have found that exaggerated responses of the immune system explain why the elderly succumb to viral infections more readily than younger people.
Women at risk from vitamin A deficiency
Almost half of UK women could be suffering from a lack of vitamin A due to a previously undiscovered genetic variation, scientists at Newcastle University have found.
Immune system activated in schizophrenia
Researchers at the Swedish medical university Karolinska Institutet have discovered that patients with recent-onset schizophrenia have higher levels of inflammatory substances in their brains. Their findings offer hope of being able to treat schizophrenia with drugs that affect the immune system.
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