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7.13:

Retroviruses

JoVE Core
Molecular Biology
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JoVE Core Molecular Biology
Retroviruses

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Transposition is widely used by a variety of pathogens to hijack the host cell’s genome.  One class of deadly pathogens that uses this process is called a retrovirus. Outside the host cell, a retrovirus exists as a retrovirus exists as a lipid enveloped, core protein shell or capsid.  The capsid contains viral proteins and enzymes and a dimeric RNA genome that encodes three major protein types.  The first are group-specific antigen or “gag” proteins that form the core structure of the viral particle. The second set code for envelope proteins that recognize specific host cell surface receptors and enable binding. Finally, it includes genes encoding Pol proteins – including a reverse transcriptase enzyme, an integrase, and RNase H. When infecting a cell, the retrovirus fuses its lipid envelope with the host cell membrane. Once inside the cell, the protein capsid is lost, and the viral reverse transcriptase transcribes the viral genomic RNA into a single-stranded DNA that binds to the viral RNA as a DNA/RNA duplex.  Next, RNase H degrades the RNA template, and the reverse transcriptase synthesizes the complementary DNA strand – creating a double-stranded DNA copy of the viral genome known as proviral DNA. Next, the viral enzyme integrase cleaves the host DNA and attaches the proviral DNA into the host genome. Retroviruses can be classified as endogenous, or exogenous. Endogenous retroviruses are non-pathogenic – remaining in the cell as a harmless transposable element. The human genome contains between 100–1,000 copies of such viruses.  The second group, Exogenous retroviruses or “exoviruses,” are pathogens. They enter a cell and take advantage of the host cell’s replication and translation machinery to create more copies of the virus and produce the virus-encoded proteins. Well-known examples of these include the AIDS virus, T-cell leukemia, and Hepatitis B.

7.13:

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’ terminal and has a polyadenylated 3’ end. Thus, the host cell’s ribosome translates the retroviral mRNA into a single chain of polyproteins. Some retroviruses use virus-encoded proteases to process this single chain into the proteins required for virion assembly. The retroviral mRNA is then packaged into a core with gag proteins, encapsulated by capsid proteins. For the release of the virus from the cell, a part of the host cell membrane's lipid bilayer is pinched off to form the outer shell of the virus. The assembled virus particle is then released to carry on the cycle of infection.

The transposition-like events in the life cycle of retroviruses are not coincidental. Present-day retroviruses are proposed to have evolved from the foamy virus, an ancient line of retroviruses that lived in the ocean. Vertebrates such as fish contained retrotransposons of genes encoding envelope proteins that captured the foamy viruses.

The close relationship between retrotransposons and retroviruses exist even today. The main distinguishing factor between the two is that although retrotransposons can form capsid proteins, they cannot synthesize viral envelopes. Therefore, no mature virus particles are formed, and the retrotransposons cannot be horizontally transferred from one cell to another.

Sequencing the human genome has revealed that 8% of the human genome contains retroviral elements, though they are in a latent state. These elements are considered to be “fossils” of ancient retroviruses and are immensely helpful in understanding not only viral but vertebral evolution as well.

Suggested Reading

  1. Krebs, Jocelyn E., Elliott S. Goldstein, and Stephen T. Kilpatrick. Lewin's genes X. Jones & Bartlett Publishers, 2009.
  2. Aiewsakun, Pakorn, and Aris Katzourakis. "Marine origin of retroviruses in the early Palaeozoic Era." Nature communications 8 (2017): 13954.