Retroviruses

Retrovirus definition

Viruses are classified by their shape, genome, and mode of replication.² Viruses vary in the genetic material that they contain. A virus’ genome can be single- or double-stranded and it can be composed of RNA or DNA.

Retroviruses consist of two single-stranded RNA segments, a capsid, and an envelope.² Retroviruses were named so because they contain reverse transcriptase.³ They transcribe their RNA genome into DNA, the opposite of the usual order of gene expression. Generally, DNA is transcribed into RNA, then translated into protein. In retroviruses, the first order of the first step is flipped.

Retrovirus examples

There are many kinds of retroviruses. Retroviruses are classified into three families: Oncoviruses, Lentiviruses, and Spumaviruses (you do not need to know these names).⁴ Retroviruses are also classified based on morphology.⁴ The most famous, or infamous, retrovirus is the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). Another well-known retrovirus is the human T cell leukemia virus (HTLV), which can cause leukemia.⁴

Figure 3. HIV structure, sourced from Wikimedia Commons

HIV infects the body’s white blood cells, the primary cells of the immune system. HIV infects these cells, specifically CD4 T lymphocytes, and kills them at the end of its replication cycle when virions are released. As a result, HIV infection makes the body more susceptible to other infections and diseases. In fact, it is not HIV that kills people, but these opportunistic infections that take advantage of the severely weakened immune system (Fig. 3).

There are three stages of HIV infection. Infection begins with an acute infection that lasts days to weeks.⁴ It progresses to a chronic infection that can last decades before progressing to AIDS, the most severe form of HIV infection.⁴ AIDS has a survival time of a few years without treatment.⁴ Treatment can prevent progression to AIDS.⁴ HIV infection has no cure, but treatment is very effective.

HTLV was the first retrovirus discovered,⁵ although it is much less common than HIV. HTLV was also the first oncogenic, or cancer-causing, retrovirus discovered.⁶ Like HIV, HTLV is transmitted through contact with infected bodily fluids.⁶ HTLV infection is usually asymptomatic or results in no symptoms or disease.⁶ In rare instances, HTLV infection can result in cancer (leukemia or lymphoma), skin disorders, nervous system disorders, or other medical conditions.⁶

Another retrovirus that has become rampant over the years is SARS-COV-2. This virus causes the disease COVID-19 and can be very deadly to certain subpopulations. The SARS-COV-2 virus enters the host cells through the Angiotensin Converting Enzyme 2 (ACE2) receptor. Once inside the cell, the virus binds to specialized receptors called Toll-Like Receptors. These receptors function to alert the host's immune system that a foreign virus is present.

The body's first line of defense is the innate immune system. As a virus takes over a cell, transcription factors such as Nf-kb translocate to the nucleus and alter the host cell's gene expression to make the cell produce cytokines needed to fight the viral infection. Cytokines such as IL6 and TNF-a are pro-inflammatory cytokines that function to mediate the body's antiviral response. Retroviruses like SARS have evolved ways to evade the immune system's protocols and detection, which can lead to widespread infection within the host.

Endogenous retrovirus

Human endogenous retroviruses are inherited genetic elements that became a part of our genome as the result of infections throughout human evolution. Retroviruses can be classified as exogenous and endogenous based on their transmission. Endogenous retroviruses are proviruses, while exogenous retroviruses, like HIV, are what we usually think of when we think of retroviruses.⁴ Exogenous retroviruses are infectious, while endogenous viruses are not infectious and are often incomplete or otherwise defective viruses.⁴

Retrovirus life cycle/retrovirus replication

The retrovirus life cycle is divided into two phases, early and late.¹⁰ The early phase consists of the initial steps from the retrovirus binding to the host cell to the viral cDNA integrating into the cell's genome.¹⁰ The late phase consists of the steps from the expression of viral genes to the release of virions.¹⁰ The viruses use the host cell's molecules, proteins, and machinery to replicate.

Figure 5. Retrovirus life cycle, including replication; sourced from Wikimedia Commons

The first step of the retrovirus life cycle is binding.¹⁰ During this step, the retrovirus binds to the target cell (Fig. 5, Step 2).¹⁰ After binding, viral envelope proteins interact with specific receptor proteins on the host cell's surface so the retrovirus can enter the target cell (Fig. 5, Step 3).¹⁰ Most retroviruses enter by fusion with the target cell; the envelope fuses with the plasma membrane of the target cell and the viral core, composed of RNA and protein protected by a capsid, enters the cytoplasm target cell. The capsid of the core degrades, releasing the RNA and proteins.

In the cytoplasm, reverse transcriptase converts the RNA genome to complementary DNA (cDNA) strands (Fig. 5, Step 4).¹⁰ The cDNA is replicated to create double-stranded DNA sequences (Fig. 5, Step 5).¹⁰ This DNA then travels to the nucleus, inserting itself into the host cell's genome (Fig. 5, Step 6).¹⁰ Once a part of the genome, the viral DNA can be transcribed into RNA to serve as the genome of virions and messenger RNA (mRNA) to be translated into viral proteins (Fig. 5, Steps 7-8). The virions are assembled in the host cell cytoplasm and released by budding through the cell plasma membrane, acquiring an envelope in the process (Fig. 5, Step 9).¹¹