Retroviruses are a family of viruses that store their genetic material as ribonucleic acid (RNA) rather than deoxyribonucleic acid (DNA). The “retro” in their name refers to their ability to reverse the typical flow of genetic information within a cell. While most organisms convert DNA into RNA, retroviruses convert their RNA into DNA, allowing them to integrate their genetic code into a host cell’s genome. This enables them to persist within an infected organism.
How Retroviruses Replicate
Retroviruses replicate by attaching to specific receptors on the surface of a host cell, then entering the cell and releasing their viral RNA and associated enzymes into the cytoplasm. Once inside, an enzyme, reverse transcriptase, converts the single-stranded viral RNA into a double-stranded DNA copy, often referred to as complementary DNA (cDNA).
The newly synthesized viral DNA then travels into the host cell’s nucleus. Here, another viral enzyme, integrase, inserts this viral DNA directly into the host cell’s own DNA, making it a permanent part of the host’s genetic blueprint. This integrated viral DNA is now called a “provirus.” The host cell treats this provirus as its own genetic material, transcribing and translating the viral genes along with its own. This leads to the production of new viral RNA and proteins, which then assemble into new retroviral particles that bud off from the host cell, infecting other cells.
Common Retroviral Diseases
Retroviruses are responsible for several diseases, with the Human Immunodeficiency Virus (HIV) being the best known. HIV, a lentivirus, causes Acquired Immunodeficiency Syndrome (AIDS) by primarily targeting and destroying CD4+ T-cells, a type of white blood cell important for immune function. The progressive loss of these cells weakens the immune system, making individuals susceptible to opportunistic infections and certain cancers.
Human T-lymphotropic virus type 1 (HTLV-1) is another retrovirus. HTLV-1 causes a lifelong infection and can lead to serious conditions in a small percentage of infected individuals, typically 5-10%. These conditions include Adult T-cell Leukemia/Lymphoma (ATL), a form of blood cancer, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive neurological disorder affecting the spinal cord. While HTLV-1 also infects T-cells, it generally does not destroy them like HIV, and most infected individuals remain asymptomatic for decades.
Treating Retroviral Infections
Treating retroviral infections involves antiretroviral therapy (ART), particularly for HIV. ART employs a combination of drugs that target different stages of the retroviral life cycle, aiming to reduce the viral load in the body, preserve immune function, and prevent disease progression. These medications do not cure the infection but manage it effectively, significantly improving the quality of life for infected individuals and preventing transmission.
Specific classes of ART drugs inhibit various viral enzymes or processes. For example, nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) block the reverse transcriptase enzyme, preventing the conversion of viral RNA into DNA. Other drug classes, such as protease inhibitors and integrase inhibitors, interfere with the assembly of new viral particles or their integration into the host genome, respectively. Beyond treatment, pre-exposure prophylaxis (PrEP) involves HIV-negative individuals taking antiretroviral medications to significantly reduce their risk of acquiring HIV through sexual contact.
Retroviruses in Biotechnology
Despite their association with diseases, retroviruses are valuable tools in biotechnology and gene therapy due to their ability to integrate their genetic material into host DNA. Scientists can modify retroviruses by removing their disease-causing genes and replacing them with therapeutic genes. These engineered retroviruses then act as “vectors” to deliver the desired genetic material into target cells.
This application is useful in gene therapy, where retroviral vectors can introduce functional copies of genes into cells to correct genetic defects or add new functions. For example, they have been explored for treating severe combined immunodeficiency (SCID) and various cancers by delivering genes that can stimulate an immune response or replace missing proteins. The stable integration of the delivered gene into the host cell’s genome ensures long-term expression, making retroviruses an asset in developing new medical treatments and understanding gene function.