What are retroviruses?

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Ribonucleic acid (RNA) viruses that replicate by synthesizing a double-stranded deoxyribonucleic acid (DNA) molecule that integrates into the host genome. They are known to infect virtually all animals and sometimes cause serious disease, including cancer.
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Biology of Retroviruses

Retroviruses are members of the viral family Retroviridae. They are enveloped, positive sense (+) RNA viruses about 100 nanometers in diameter that replicate within the host’s cytoplasm through a double-stranded DNA intermediate that is integrated into the host genome. In addition to the +RNA, there is a cellular tRNA hydrogen bonded to the +RNA that serves as a primer for reverse transcriptase.

The viral RNA genome, its associated nucleoprotein, reverse transcriptase, and integrase are surrounded by a protein capsid. Immediately external to the capsid is the matrix protein. The outer layer of the retrovirus is a lipid bilayer envelope derived from the host’s plasma membrane that is acquired as the virus emerges from the host cell. Within the envelope are two glycoproteins that are encoded by the virus genome and serve as plasma membrane attachment sites during entry into the cell.

The retrovirus genome consists of two 7 kilobase to 11 kilobase +RNA molecules that code for only a few proteins, including gag, which codes for the matrix, capsid, and nucleoprotein; pol, which codes for reverse transcriptase, RNAse, integrase, and a protease; and env, which codes for the envelope glycoproteins.

The retrovirus binds to plasma membrane receptors via the viral envelope glycoproteins. When the retrovirus enters the cell, the viral RNA is released along with its reverse transcriptase. A double-stranded DNA is synthesized from the +RNA using viral reverse transcriptase. Integrase catalyzes the incorporation of the double-stranded DNA molecule into the host genome. When integrated, the viral DNA is referred to as a provirus and replicates with the host genome. Host RNA polymerase transcribes the viral genes, making copies of the viral genome and mRNA molecules that can be translated into viral proteins. Viral RNA and proteins are assembled into new viral particles that emerge from the plasma membrane by budding.

Some retroviruses such as Rous sarcoma virus (RSV), feline leukemia virus (FLV), and mouse mammary tumor virus (MMTV) can induce tumors in their host species. More than twenty-five cancer-causing (oncogenic) retroviruses have been isolated. The retrovirus gains oncogenic potential when it inadvertently acquires a eukaryotic gene during infection. Although the eukaryotic gene may not be oncogenic when first acquired, after several generations it may mutate or otherwise become altered, transforming it into one that is oncogenic. Retroviruses such as FLV that do not carry an oncogene can still transform by either disrupting the function of a normal gene by integrating within it or by integrating next to it so that the neighboring gene can use the viral promoter, resulting in gene overexpression and cellular proliferation.

Perspective and Prospects

The study of retroviruses dates to 1910 with the work of Peyton Rous, who discovered that certain sarcomas in chickens are caused by an agent later identified as a virus. The virus was later named Rous sarcoma virus. In 1970, the laboratories of Howard Temin and David Baltimore independently discovered that certain RNA viruses have an enzyme, now known as reverse transcriptase, that permit the viruses to reverse transcribe their RNA genomes into double-stranded DNA. In the early 1970s, the laboratory of J. Michael Bishop and Harold Varmus demonstrated that Rous sarcoma virus has a gene, now known as src, responsible for transforming normal cells into tumor cells. Uninfected cells, including human cells, have a normal src gene that is related to the viral src gene. In the past, an RSV infected a chicken and incorporated the host src gene into its own genome. The src gene acquired by the virus became altered over time so that it now causes cancer when an RSV infects a chicken cell.

There are many examples of retroviruses, including human T-cell leukemia virus (HTLV), the first pathogenic human retrovirus discovered in 1980 by Bernard J. Poiesz, Robert Gallo, and their colleagues at the National Institutes of Health and by Mitsuaki Yoshida in Japan. Human immunodeficiency virus (HIV), which causes Acquired immunodeficiency syndrome (AIDS), is also a retrovirus; it was discovered in 1983 by Luc Montagnier, Françoise Barré-Sinoussi, and their colleagues at the Pasteur Institute in France.

Since reverse transcriptase does not have the proofreading activities associated with DNA polymerase, retroviruses mutate and evolve more rapidly than DNA viruses, making the development of drugs and vaccines difficult.

Recombinant retroviruses are often used as vectors for genetic engineering. Retroviruses that are modified by removing the genes that make them harmful and replacing them with normal eukaryotic genes can be used to deliver a normal copy of a gene to a defective cell. The DNA copy of the recombinant retrovirus can integrate into the host genome and genetically modify the cell.


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