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An Approach to Define Molecular Biology of Leukemia Virus  
 
Leukemia virus
Leukemia virus is a mammalian single stranded RNA retrovirus that causes T and B- cell leukemia and T and B - cell lymphoma in adults and may also be involved in certain demyelinating diseases, including tropical spastic paraparesis. Leukemia virus contains viral RNA and several copies of reverse transcriptase (DNA polymerase). After infecting a cell, the reverse transcriptase is used to make the initial copies of viral DNA from viral RNA. Once a DNA strand has been synthesized, a complementary viral DNA strand is made. These double strand copies of viral DNA are inserted into the host-cell chromosome and host-cell RNA polymerase is used to make virus-related RNA. These RNA strands serve as templates for making new copies of the viral chromosomal RNA and serve also as mRNA. mRNA is translated into viral proteins that are used to make the virus envelope. New viral particles are assembled, bud from the plasma membrane, and are released for a new virus particle.

Retrovirade Family:
The retrovirade family contains the Abelson murine leukemia virus, Bovine leukemia virus, Feline leukemia virus, Friend murine leukemia virus, Gibbon ape leukemia virus, Molony murine leukemia virus, Rauscher murine leukemia virus. A retroviridae family contains a virus which has a genome consisting of two identical plus sense RNA molecules. The gammaretroviruses deltaretrovirus represent a group of mammalian oncogenic retroviruses typically associated with the induction of leukemia and lymphoma in the natural host. Shown the variety of these genuses of viruses.

The retrovirus life cycle:

The retroviral life cycle begins in the nucleus of an infected cell. At this stage of the life cycle the retroviral genome is a DNA element integrated into and covalently attached to the DNA of the host cell. The genome of the virus is of approximately 812 kilo bases of DNA (depending upon the retroviral species). Full-length genomic mRNA is made nitiating at the beginning of the R (repeat) at the 5' LTR (Long Terminal Repeat).The free particle can infect new cells by binding to a cell surface receptor. The specificity of the virus cell interaction is determined largely by the envelope protein(s) of the retrovirus. Infection leads to injection of the virus nucleoprotein core (consisting mostly of gag derived proteins, full-length genomic RNA, and the reverse transcriptase protein).
Once inside the cell, the nucleoprotein complex accesses intracellular DNA nucleotide riphosphate pools, whereupon the reverse transcriptase protein initiates creation of a double stranded DNA copy of the genome of the virus in preparation for integration into the host cell chromosome. Upon completion of reverse transcription, the viral enzyme Integrase searches the DNA for an appropriate "home", whereupon the integrase clips the host DNA and sews the Double stranded DNA into the host DNA (see below). The virus is now prepared to initiate a new round of replication.

Fig: Life cycle of tumor retrovirus (leukemia virus)
 
Major Proteins of Retroviral Genome (gag, pol and env):
Retrovirus genomes commonly contain these three open reading frames that encode for proteins that can be found in the mature virus:

Gag processed to matrix and another core protein that determine retroviral core. ( Gag is a polyprotein and is an acronym for Group Antigens (ag).).
Pol Reverse transcriptase, RNase H and integrase functions.
Env envelop protein; reside in lipid layer; determine viral tropism.

Fig: Three major protein in tumor retrovirus (Leukemia virus)
 
The group antigens form the viral core structure, RNA genome binding proteins, and are the major proteins comprising the nucleoprotein core particle. Reverse transcriptase is the essential enzyme that carries out the reverse transcription process that take the RNA genome to a double stranded DNA preintegrate form. The molecular gymnastics of the latter process are outlined below. The reverse transcriptase gene also encodes an Integrase activity and an RNase H activity that functions during genome reverse transcription.

The seven varieties of leukemia virus are used in this database. These are as follows:
Abelson murine leukemia virus (NC 001499)
Bovine leukemia virus (NC 001414)
Feline leukemia virus (NC 001940)
Friend leukemia virus (NC 001362)
Gibbon ape leukemia virus (NC 001885)
Molony murine leukemia virus (NC 001501)
Rauscher murine leukemia virus (NC 001819)

Abelson Murine Leukemia Virus
The Abelson murine leukemia virus (A-MuLV) is a retrovirus (Class VI) used to induce transformation of murine lymphoid cells. The Abelson murine leukemia virus is named for the American pediatrician Herbert T. Abelson who first described and isolated it. 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 have determine 5,894 nucleotide structure in genome. The coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet. A-MuLV causes a rapidly progressive lymphosarcoma known as Abelson disease in mice, which is a type of leukemia.

Bovine leukemia virus
In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia The Bovine leukemia virus have determine 8,1419 nucleotide structure in genome. The coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet. In general BLV under natural conditions the disease is transmitted mainly by milk to the calf. Infected blood cells transmit the disease too. So for artificial infection infected cells are used or the more stable and even heat resistant DNA. Virus particles are difficult to detect and not used for transmissing of infection. It is possible that a natural virus reservoir exists in the water buffalo.

Feline leukemia virus
Feline leukemia virus (FeLV), a retrovirus, so named because of the way it behaves within infected cells. The Feline leukemia virus have determine 8,448 nucleotide structure in genome. The coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet. FeLV is usually transmitted between infected cats when the transfer of saliva or nasal secretions is involved, for example when sharing a feeding dish. If not defeated by the animal's immune system, the virus can be lethal.

Friend murine leuekemia virus
The Friend virus is a strain of murine leukemia virus identified by Charlotte Friend in 1956. The Friend murine leukemia virus have determine 8,328 nucleotide structure in genome. The coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet. The helper-independent virus Friend leukemia virus (F-MuLV) is an ecotropic retrovirus that induces erythroleukemia at a high rate in newborn mice and lymphatic leukemia with a long latency in adult mice.The virus infects adult immunocompetent mice and is a well-established model for studying genetic resistance to infection by an immunosuppressive retrovirus.The Friend virus has been used for both immunotherapy and vaccines.

Gibbon ape leukemia virus
Gibbon ape leukemia virus (GaLV) is a highly oncogenic C-type retrovirus capable of inducing myeloid leukemia in juvenile gibbons. GaLV is antigenically most closely related to a new world monkey virus, simian sarcoma associated virus (SSAV), and less to the murine and feline C-type leukemia viruses. Young gibbons that were experimentally inoculated with cell-free gibbon ape leukemia virus (GaLV) and developed peristent viremia subsequently developed chronic granulocytic leukemia (CGL) with associated multifocal bone lesions and metastases.

Molony murine leukemia virus
This is wild type oncogenic in mice. It is single stranded, linear RNA genome. The Molony murine leukemia virus have determined the 8,332-nucleotide structure in the genome The coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet. The pol gene encodes 132,000 daltons of protein, larger than the 70,000 daltons required for the reverse transcriptase. The env gene overlaps the pol gene.

Rauscher murine leukemia virus
The Rauscher murine leukemia virus that can infection of a rat kidney cell line. The Rauscher murine leukemia virus have determine 8,282 nucleotide structure in genome. The coding frame for the gag gene is the same as that for pol, separated only by a single amber triplet. The complete nucleotide sequence of the genome of Rauscher murine leukemia virus (R-MuLV), the replication-competent helper virus present in the Rauscher virus complex, and its phylogenetic relationship with other murine leukemia virus genomes. An overall sequence identity of 97.6% was found between R-MuLV and the Friend helper virus (F-MuLV), and the two viruses were closely related on the phylogenetic trees constructed from either gag, pol, or env sequences.

 


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