Retroviruses represent a distinct category of viruses. Unlike most organisms and viruses that store their genetic information as DNA, retroviruses utilize RNA as their primary genetic material. When a retrovirus infects a cell, it must first convert its RNA genome into DNA, a process that goes against the typical flow of genetic information. This reversal is central to their classification and operation.
The Unique Process of Reverse Transcription
The defining feature of retroviruses is their reliance on an enzyme called reverse transcriptase. This enzyme converts the viral RNA genome into a DNA copy once the virus enters a host cell. This process is termed “reverse transcription” because it inverts the conventional biological process where DNA is transcribed into RNA.
Reverse transcriptase possesses multiple activities, including RNA-dependent DNA polymerase activity, which synthesizes a DNA strand from the RNA template. It also has ribonuclease H (RNase H) activity to degrade the original RNA template. These combined actions result in a double-stranded DNA molecule from the single-stranded viral RNA. Without reverse transcriptase, retroviruses cannot integrate their genetic material into the host cell’s genome, preventing replication. This enzyme is a primary target for antiviral therapies.
How Retroviruses Operate
The replication cycle of a retrovirus begins with its entry into a host cell. The virus binds to specific receptors on the host cell’s surface, fusing its envelope with the cell membrane and releasing its core into the cytoplasm. Once inside, the viral RNA genome and associated enzymes, including reverse transcriptase, are released.
Following reverse transcription, the newly synthesized double-stranded viral DNA travels to the host cell’s nucleus. Here, another viral enzyme called integrase inserts this viral DNA into the host cell’s chromosomal DNA. The integrated viral DNA is then referred to as a “provirus,” becoming a permanent part of the host cell’s genetic material.
The host cell’s machinery subsequently transcribes the proviral DNA into new viral RNA molecules. These RNA molecules serve as templates for both new viral genomes and messenger RNA for viral protein synthesis. Finally, new viral components assemble near the cell surface and bud off, acquiring a portion of the host cell membrane as their outer envelope, ready to infect other cells.
Major Retroviruses and Their Impact
Human Immunodeficiency Virus (HIV) is the most widely known retrovirus affecting humans. HIV targets immune cells, particularly CD4 T cells, which are components of the body’s defense system. By infecting and destroying these cells, HIV weakens the immune system, leading to acquired immunodeficiency syndrome (AIDS).
Other human retroviruses include Human T-lymphotropic Virus type 1 (HTLV-1) and type 2 (HTLV-2). HTLV-1 is associated with adult T-cell leukemia and a neurological disorder known as HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-2 has a weaker association with human disease but may cause neurological symptoms. These retroviruses are transmitted through sexual contact, blood exposure, or from mother to child, impacting millions globally.
Addressing Retroviral Infections
Managing retroviral infections involves therapeutic strategies that target specific stages of the viral life cycle. Antiretroviral therapies (ART) inhibit enzymes like reverse transcriptase, integrase, and protease, which are essential for viral replication. For instance, reverse transcriptase inhibitors prevent the conversion of viral RNA into DNA, while integrase inhibitors block the insertion of viral DNA into the host genome.
These treatments effectively control the viral load, reducing the amount of virus in the body and protecting the immune system. However, because the viral DNA integrates into the host cell’s genome, current therapies cannot eradicate the virus from the body. Therefore, individuals with retroviral infections often require lifelong treatment to manage the condition and prevent disease progression.