Retrovirus

The specialized DNA-infiltration enzymes in retroviruses make them valuable research tools in molecular biology, and they have been used successfully in gene delivery systems.

The pol region encodes enzymes necessary for viral replication, such as reverse transcriptase, protease and integrase.

However, many endogenous retroviruses play important roles in host biology, such as control of gene transcription, cell fusion during placental development in the course of the germination of an embryo, and resistance to exogenous retroviral infection.

The term "retro" in retrovirus refers to this reversal (making DNA from RNA) of the usual direction of transcription.

Reverse transcriptase activity outside of retroviruses has been found in almost all eukaryotes, enabling the generation and insertion of new copies of retrotransposons into the host genome.

These two glycoprotein products stay in close affiliation, and they are transported to the plasma membrane after further glycosylation.

[3] It is important to note that a retrovirus must "bring" its own reverse transcriptase in its capsid, otherwise it is unable to utilize the enzymes of the infected cell to carry out the task, due to the unusual nature of producing DNA from RNA.

[citation needed] Industrial drugs that are designed as protease and reverse-transcriptase inhibitors are made such that they target specific sites and sequences within their respective enzymes.

[citation needed] Because reverse transcription lacks the usual proofreading of DNA replication, a retrovirus mutates very often.

This enables the virus to grow resistant to antiviral pharmaceuticals quickly, and impedes the development of effective vaccines and inhibitors for the retrovirus.

This gives rise to a concern that insertional mutagenesis due to integration into the host genome might lead to cancer or leukemia.

This is unlike Lentivirus, a genus of Retroviridae, which are able to integrate their RNA into the genome of non-dividing host cells.

[citation needed] Two RNA genomes are packaged into each retrovirus particle, but, after an infection, each virus generates only one provirus.

[15] LTRs are able to send signals for vital tasks to be carried out such as initiation of RNA production or management of the rate of transcription.

[citation needed] Studies of retroviruses led to the first demonstrated synthesis of DNA from RNA templates, a fundamental mode for transferring genetic material that occurs in both eukaryotes and prokaryotes.

[citation needed] An estimate of the date of evolution of the foamy-like endogenous retroviruses placed the time of the most recent common ancestor at > 450 million years ago.

This technology is of use, not only for research purposes, but also for clinical gene therapy aiming at the long-term correction of genetic defects, e.g., in stem and progenitor cells.

Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases.

Rous sarcoma virus contains the src gene that triggers tumor formation.

Nontransforming viruses can randomly insert their DNA into proto-oncogenes, disrupting the expression of proteins that regulate the cell cycle.

In addition to the usual gene sequence of retroviruses, HTLV-1 contains a fourth region, PX.

The Tax protein initiates the leukemic process and organizes the transcription of all viral genes in the integrated HTLV proviral DNA.

[32] Both families in Group VII have DNA genomes contained within the invading virus particles.

Virally encoded reverse transcriptase uses the pre-genomic RNA as a template for the creation of genomic DNA.

The genomic and subgenomic organization of a prototypical retrovirus. Abbreviations are explained in the file description. [ 18 ]
A retrovirus has a membrane containing glycoproteins, which are able to bind to a receptor protein on a host cell. There are two strands of RNA within the cell that have three enzymes: protease, reverse transcriptase, and integrase (1). The first step of replication is the binding of the glycoprotein to the receptor protein (2). Once these have been bound, the cell membrane degrades, becoming part of the host cell, and the RNA strands and enzymes enter the cell (3). Within the cell, reverse transcriptase creates a complementary strand of DNA from the retrovirus RNA and the RNA is degraded; this strand of DNA is known as cDNA (4). The cDNA is then replicated, and the two strands form a weak bond and enter the nucleus (5). Once in the nucleus, the DNA is integrated into the host cell's DNA with the help of integrase (6). This cell can either stay dormant, or RNA may be synthesized from the DNA and used to create the proteins for a new retrovirus (7). Ribosome units are used to translate the mRNA of the virus into the amino acid sequences which can be made into proteins in the rough endoplasmic reticulum. This step will also make viral enzymes and capsid proteins (8). Viral RNA will be made in the nucleus. These pieces are then gathered together and are pinched off of the cell membrane as a new retrovirus (9).
Phylogeny of Retroviridae