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Retroviruses

Their Role in Human Disease and Health

Oct 9, 2009 Stephen Allen Christensen

Retroviruses are a diverse group of RNA-containing viruses that contribute to several human diseases. They may one day be exploited to cure illnesses, too.

Retroviruses are viruses that are capable of "tricking" an infected cell into incorporating the virus’ genes into the cell’s chromosome.

As the cell goes about the business of reading and translating its own DNA to perform day-to-day tasks, the viral genes are also translated; this leads to the production of new viral components that are eventually capable of infecting other cells.

Retroviruses are responsible for a variety of human diseases, including AIDS (HIV) and T-cell leukemias, lymphomas, and spastic paraparesis (HTLV-1).

Now another retrovirus, known as XMRV, has been implicated in prostate cancer and chronic fatigue syndrome. (Lombardi V, Ruscetti F, et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science [8 October, 2009],1179052)

Anatomy of a Retrovirus

While different retroviruses vary in appearance and biological activities, their structures are similar:

Envelope: a lipid bilayer which is taken from the host cell as the virus buds from the cell
Capsid: a protein coat that is surrounded by the envelope and which contains the viral genome and several proteins
Genome: the genetic material of a retrovirus is carried in two identical strands of RNA
Reverse transcriptase: an enzyme that copies the viral RNA to form a segment of double-stranded DNA. This process occurs after the virus has entered the cell
Integrase: an enzyme that splices the viral DNA segment into one of the cell’s chromosomes, where it may reside and replicate through many cellular generations. Translation of this persistent segment of DNA by cellular machinery leads to production of viral components
Other proteins: proteases, capsid proteins, and envelope proteins that contribute to viral structure, maturation, and infectivity

Retrovirus Behavior and Its Impact on Human Biology

Oddly, human cells have been invaded and co-inhabited by many retroviruses through the millennia; indeed, it is believed that 5 – 8% of the human genome is composed of so-called endogenous retroviruses. (Belshaw R, Pereira V, et al. Long-term reinfection of the human genome by endogenous retroviruses. Proc Natl Acad Sci USA 2004;101[14]:4894-99)

Most endogenous retroviral genetic material is of no apparent consequence or use; it is often called “junk DNA.” However, some of these genetic inclusions have become integral parts of human chromosomes and play a role in important cellular processes. Others – called oncogenes – have been implicated in malignant transformation, and still others may play a role in the development of autoimmune diseases.

One characteristic of retroviruses – a behavior that makes it difficult to create drugs to effectively treat those that cause disease – is the tendency for errors and substitutions to occur during the process of reverse transcription.

“Mistakes” in duplication of the viral genome are random in nature, but they lead to subtle changes in the virus that confer resistance to antiviral drugs or thwart vaccine development.

Retroviruses in the Treatment of Human Disease

Scientists have long been intrigued by the idea of using retroviruses to insert desirable genetic material into human chromosomes to treat a variety of diseases.

The potential utility of retroviral vectors (retroviruses that have been connected to “therapeutic” segments of DNA) is far-reaching. Diseases caused by abnormal genes (e.g., sickle-cell anemia) could be permanently corrected by hooking the normal gene to a retrovirus and allowing the virus to “infect” the affected person.

Retroviral vectors may also find extensive use in the development of stem cell lines that could address a myriad of human illnesses.

Unfortunately – although the science behind the construction of retroviral vectors is relatively straightforward – the long-term effects of introducing foreign genetic material into human cells are as yet unknown. Since retroviruses often act as oncogenes, it is possible that a person could be cured of a genetic defect only to develop cancer later in life.

Retroviruses can be a cause of human disease, but they are also an integral part of our genetic makeup. A great deal of research will be necessary before retroviruses find routine use in medical therapy, but the very mechanism which makes retroviral diseases difficult to treat may soon be turned to humankind’s advantage.

The copyright of the article Retroviruses in General Medicine is owned by Stephen Allen Christensen. Permission to republish Retroviruses in print or online must be granted by the author in writing.

Structure of a Retrovirus