Retroviruses

Viruses are the smallest microbe.1 Although viruses and bacteria are often lumped together, as they both can cause disease, they are very different. Unlike bacteria, viruses such as retroviruses are not living organisms. Bacteria can replicate on their own, but viruses need a host cell since they are not alive. Similar to bacteria, a wide variety of viruses vary in structure, life cycle, and components.

Retroviruses Retroviruses

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Table of contents

    A virus is composed of genetic material surrounded by a protein coat known as a capsid, which may be surrounded by a lipid membrane known as an envelope (Fig. 1).

    Retroviruses [+] virus structure [+] StudySmarterFigure 1. The structure of a virus, sourced from Wikimedia Commons

    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.

    A retrovirus is an enveloped virus with a single-stranded RNA genome and reverse transcriptase.

    Reverse transcriptase is an enzyme (the suffix "-ase" denotes an enzyme) that performs reverse transcription, transcribing RNA to DNA (Fig. 2).

    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

    In biological classification, a family is a taxonomic rank. A taxonomy is used to classify organisms based on shared characteristics. Other taxonomic ranks you may be more familiar with are species and genius. For viruses, the taxonomy is as follows (from least to most specific): order, family, subfamily, genus, and species.2

    Retroviruses [+] HIV [+] StudySmarterFigure 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

    Transcription factors are specialized proteins that regulate gene expression and can control whether a gene is expressed or not. Transcription factors like Nf-kb enhance the expression of genes encoding proinflammatory cytokines. Nf-kb is an important transcription factor involved in the innate immune response to pathogens.

    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.

    Cytokine: Specialized proteins of the immune system that function as signals for immune cells

    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

    Exogenous retroviruses are transmitted horizontally, from human to human4 (Fig. 4).

    Endogenous retroviruses are genetic material of retroviral origin (remains of exogenous retroviruses) integrated into the host species' chromosomal DNA or genome.4,8 They are transmitted vertically;4,8 they are inherited by offspring from parents like any other gene.

    A provirus is a genetic material from a virus that is integrated into the genome of the host cell.9

    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.

    Retroviruses [+] Retrovirus life/replication cycle [+] StudySmarterFigure 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

    Retroviruses - Key takeaways

    • Viruses are not living; they are parasites that need host cells to replicate.
    • A virus is composed of genetic material surrounded by a protein coat, or capsid, which may be surrounded by a lipid membrane known as an envelope.
    • A retrovirus is a virus with an RNA genome and reverse transcriptase.
    • Because they have an RNA genome, retroviruses use reverse transcriptase to transcribe RNA to DNA.
    • Two well-known retroviruses are the human immunodeficiency virus (HIV) and the human T cell leukemia virus (HTLV).

    References

    1. Microbiology Society, Viruses, n.d. https://microbiologysociety.org/why-microbiology-matters/what-is-microbiology/viruses.html
    2. Hans R. Gelderblom, Structure and Classification of Viruses (Chapter 41), In: Medical Microbiology (4th edition), 1996. https://www.ncbi.nlm.nih.gov/books/NBK8174/
    3. Retrovirus, n.d. https://www.genome.gov/genetics-glossary/Retrovirus
    4. Miles W. Cloyd MW, Human Retroviruses (Chapter 62), In: Medical Microbiology (4th edition), 1996. https://www.ncbi.nlm.nih.gov/books/NBK7934/
    5. About HIV, 1 Jun 2021. https://www.cdc.gov/hiv/basics/whatishiv.html#:~:text=HIV%20(human%20immunodeficiency%20virus)%20is,healthy%20and%20prevent%20HIV%20transmission.
    6. Recommendations for Counseling Persons Infected with Human T-Lymphotrophic Virus, Types I and II, 25 Jun 1993. https://www.cdc.gov/mmwr/preview/mmwrhtml/00021234.htm
    7. Human T-lymphotropic virus type 1, 3 Mar 2021. https://www.who.int/news-room/fact-sheets/detail/human-t-lymphotropic-virus-type-1
    8. James M. Sharp, Marcelo de las Heras, Thomas E. Spencer, Massimo Palmarini; Jaagsiekte Sheep Retrovirus, in Encyclopedia of Virology (3rd Edition), 2008. https://www.sciencedirect.com/science/article/pii/B9780123744104006750
    9. HIV/AIDS Glossary: Provirus, n.d. https://clinicalinfo.hiv.gov/en/glossary/provirus
    10. Sébastien Nisole and Ali Saïb. Early steps of retrovirus replicative cycle, Retrovirology, 14 May 2004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC421752/
    11. John Goulding, Virus replication, n.d. https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/virus-replication
    Frequently Asked Questions about Retroviruses

    What is a retrovirus?

    A retrovirus is an enveloped virus with a single-stranded RNA genome and reverse transcriptase.

    What is the function of reverse transcriptase in retroviruses?

    Reverse transcriptase transcribes RNA to DNA. 

    Which viruses are retroviruses?

    Human immunodeficiency virus (HIV) and the human T cell leukemia virus (HTLV) are examples of retroviruses. 

    Is coronavirus a retrovirus?

    Coronavirus is not a retrovirus. Although it has a single-stranded RNA genome and an envelope, it does not have reverse transcriptase.

    How is a retrovirus different from other viruses?

    Unlike other viruses, retroviruses use reverse transcriptase to perform reverse transcription, transcribing their RNA genome to DNA.

    Test your knowledge with multiple choice flashcards

    Reverse transcriptase is an enzyme that transcribes ___ to ___.

    Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) are examples of ___.

    The retrovirus life cycle is divided into two phases: ___ and ___.

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