Reverse Transcriptase and AIDS 1970 – A Revolution in Biology

According to one of biology's central dogmas, information in the sequences of DNA in our cells can be copied into RNA molecules, which can then be translated into proteins. However, in 1970, the American biologists Howard Temin and David Baltimore independently discovered reverse transcriptase (RT), an enzyme that transcribes single-stranded RNA into double-stranded DNA. This discovery led to a fuller understanding of retroviruses such as HIV (human immunodeficiency virus), which causes acquired immunodeficiency syndrome (AIDS), a disease of the human immune system.

A simple model of a retrovirus consists of an outer lipid membrane (derived from the outer membrane of an infected cell) with envelope proteins embedded in it. Inside this outer envelope is a viral protein shell surrounding two identical single-stranded RNA molecules and an RT molecule. 

When a retrovirus invades a cell: 

• First, the virus's envelope protein binds to a protein receptor on the cell surface. For example, the envelope protein of HIV subtype-1 binds to a receptor on human T cells (a type of white blood cell). 
• The virus's RT is carried inside the host cell and begins synthesizing DNA copies of the viral RNA. 
• This DNA enters the cell nucleus, and integrase (an enzyme from the virus) inserts this new DNA into the host's DNA.
• These inserts are transcribed by the host's own enzymes into new RNA molecules, which are translated into capsid proteins, RT and envelope proteins. 
• Copies of these new RNAs are incorporated into newly formed virus particles.

Drugs that inhibit RT have been developed to combat HIV. In addition, protease inhibitors can be used to block the action of the virally encoded HIV protease enzyme, which the retrovirus needs to mature properly. 

Fusion inhibitor drugs interfere with the entry of the HIV virion into a human cell, and integrase inhibitors suppress the integrase enzyme. It should also be remembered that various types of retroviruses can cause cancer when newly made viral DNA is inserted into the host DNA. 

Historical Figures Mentioned in the Article: Howard Martin Temin (1934–1994), David Baltimore (b. 1938)

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