Abelson murine leukemia virus

Abelson murine leukemia virus

Description, Causes and Risk Factors:

Abbreviation: AmuLV.

A retrovirus belonging to the Type C retrovirus group subfamily (family Retroviridae) that is associated with leukemia and induces in vitro transformation of certain mouse cells.

The Abelson murine leukemia virus (AmuLV) is a retrovirus (Class VI) used to induce transformation of murine lymphoid cells. As a retrovirus, it has a single-stranded, positive-sense RNA genome which replicates via a DNA intermediate-mediated by a reverse transcriptase. The Abelson murine leukemia virus is named for the American pediatrician Herbert T. Abelson, who first described and isolated it.

AmuLV causes a rapidly progressive lymphosarcoma known as Abelson disease in mice, which is a type of leukemia that does not involve the thymus. However, this is only possible when the host cell is co-infected with a helper virus which provides functions it needs to be able to replicate which it does not code for in its own genome such as a reverse transcriptase and some major structural proteins. As such, AmuLV can be described as a dependovirus. A highly efficient helper virus commonly used when growing AmuLV in vitro is Moloney murine leukemia virus (AmuLV). It causes leukemia directly by interfering with the normal growth and differentiation processes of lymphocytes. It can infect B-cells which was shown by the fact that some tumor cells can be seen to have immunoglobulins (Ig) on their surface although most tumor cells do not have characteristic receptors on their surface indicating that they are undifferentiated cells. In vitro studies have shown that lymphocyte infection produces tumor cell populations comprising three types of cells: stable productive cells, non-productive cells and cells which produced defective virus particles which are not infective.

AmuLV is unique among murine retroviruses in its ability to transform both fibroblasts and lymphoid cells stably in vitro. The only AmuLV-encoded gene product that has been identified rigorously is a large phosphoprotein that mediates the transfer of the y phosphate of ATP to tyrosine residues on this protein in vitro. This enzymatic activity is similar to an activity associated with Rous sarcoma virus-encoded pp60arc protein and polyoma middle T antigen.

There is sufficient evidence that the AmuLV protein is a tyrosine-specific protein kinase. There are methods for detecting this kinase activity and this kinase has been expressed in E. coli. Because the information coding for the tyrosine-specific protein kinase is present in normal mouse cells, such an enzyme must have a normal physiologic function. The elucidation of this physiologic function and the understanding of the role of this enzyme activity in neoplastic transformation is the challenge of the future.

Symptoms:

This strikes you as a flu-like sickness usually about 2 to 4 weeks following initial infection. It is estimated 50% to 90% of persons infected will get this syndrome. The most common symptoms are fever (fever means 100?F or higher), sore throat, swollen glands in the neck, armpits and groin, muscle and joint pains, rash and/or night sweats. Less common symptoms include weight loss (10 to 15 pounds), diarrhea, nausea, headache, and very rarely yeast infections of the mouth (thrush). Respiratory things like runny nose, sinus infection, coughing, sneezing, etc. are not generally considered symptoms of this syndrome.Neurological problems such as confusion, memory loss, visual disturbance, anxiety, and sleep disorder may also occur.

Diagnosis:

Antigens coded by genes of the various retroviruses can be serologically crossreactive in ELISA tests; thus it is important to utilize an assay that can discriminate between antibodies to specific proteins. The most frequently used of these tests is the Western blot test (WB). Other supplementary tests available include IFA (immunofluorescent assay) and radioimmunoprecipitation (RIPA). In contrast to IFA, WB and RIPA detect antibodies to the specific viral gene products that have been separated by gel electrophoresis. Antibodies to retroviral gene products that are routinely used in laboratory diagnosis. Products of the tat gene are regulatory proteins which affect the level of expression of other viral genes.

To examine the expression of the cellular homolog of the Abelson murine leukemia virus transforming gene (the v-abl sequence), a DNA probe representing the v-abl sequence was prepared. The probe detected two cytoplasmic polyadenylic acid-containing c-abl RNAs of about 6.5 and 5.5 kilobases in a variety of rodent cells, and slightly larger RNAs were detected in human cells. These two RNA species were found in all normal tissues or cell lines examined, but at differing concentrations: liver cells had the least, fibroblastic cell lines had the most. By using a probe able to detect the cellular but not the viral gene, the two RNAs were shown to be present in Abelson murine leukemia virus-transformed cells at levels found either in their untransformed counterparts or in similar cell types transformed by other means. The target cells of the virus have a somewhat elevated level of the two RNAs although expression of the c-abl gene is not restricted to these cells. The v-abl sequence lacks 0.35 and 0.85 kilobases of the c-abl RNA on the 5' and 3' ends, respectively. Thus, the Abelson murine leukemia virus transforming gene is an internal fragment of the transcript of a normal cellular gene.

Treatment:

Antiretroviral drugs are medications for the treatment of infection by retroviruses. Different classes of antiretroviral drugs act on different stages. Combination of several (typically three or four) antiretroviral drugs is known as highly active anti-retroviral therapy.

RESEARCH: Mouse Retroviruses ruled out as Cause of Chronic Fatigue Syndrome (CFS).

The once-promising belief that 2 retroviruses that cause leukemia in mice are potential causes of chronic fatigue syndrome (CFS) in humans has been dismissed by findings from the most rigorous study to date on the link. In the study, published in mBio, researchers found no evidence of infection with either xenotropic murine leukemia virus-related virus (XMRV) or polytropic murine leukemia virus (pMLV) infection in 147 patients with CFS.

CFS is a disabling disorder characterized by persistent unexplained fatigue in association with impaired memory or cognition, muscle or joint pain, headache, sore throat, tender lymph nodes, and night sweats. In the United States, an estimated 42 people out of 10?000 have the condition, which results in annual direct medical costs as high as $7 billion.

abelson murine leukemia virus

For years, the existence of the condition has been met with skepticism by some in the medical community because of a lack of biological explanation for the disorder. An explanation, proposed in a 2009 article published in Science that linked XMRV to the syndrome, gave hope to those with the condition that it might be treated with drugs that are used to treat HIV, another infection cause by a retrovirus. Another study, published in early 2010 in the Proceedings of the National Academy of Sciences (PNAS), reported detecting pMLV in patients with chronic fatigue syndrome, which further bolstered the theory that the condition might be caused by a mouse virus. But the inability of other laboratories and the original researchers to replicate the XMRV or pMLV association with chronic fatigue syndrome lead to the Science article being retracted in December 2011.

In the mBio study, researchers (including some who worked on the original Science and PNAS studies) recruited 147 patients with CFS and 146 matched controls from 6 sites across the United States. The patients with CFS were between the ages of 18 and 70 years; had never suffered from another neurologic or psychiatric illness; had symptoms of a viral infection prior to the syndrome's onset; had reduced a quality of life; and were not pregnant, lactating, or less than 3 months postpartum. Blood samples from those with CFS and the control group were collected for blinded analysis of XMRV, pMLV, or both using molecular, culture, and serological methods. The study was commissioned by the National Institute of Allergy and Infectious Diseases.

NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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