Julianne Edwards. Retroviruses. Spring 2010

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Candice Wilkins
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1 Retroviruses Spring 2010

2 A retrovirus can simply be referred to as an infectious particle which replicates backwards even though there are many different types of retroviruses. More specifically, a retrovirus is an RNA virus that had RNA rather than DNA as its genetic material. 1 Retroviruses have been studied and discoveries have been being made since the early nineteen hundreds. Since first being researched, it is evident that throughout all the different types of retroviruses, there are eight specific proteins and a general replication cycle that demonstrates how retroviruses infect host cells. On the other hand, specific retroviral classes demonstrate certain particle features. These shared particle features help group retroviruses by their shapes, characteristics, and ways of infection. This draws away from the general notion of the replication cycle and shows the difference between how each retrovirus infects its host as shown through the specific retrovirus, human immunodeficiency disease. In 1908, Ellerman and Bang were searching for an infectious disease (bacterium) which could be explained as the cause for leukemia. By the end of their search, the two males were able to transfer the disease from one chicken to another by cell-free tissue filtrates. The following year, in 1909, Paul Ehrlich proposed his theory of the immune surveillance. Ehrlich s immune surveillance noted that tumor cells frequently emerged into the organism thus was rapidly eliminated by the immune system. After another year passed, Peyton Rous used chickens as well to practice the transport of solid tumors. Although, Rous did it differently considering he transplanted the tissues but isolated the infectious agents as well. After approximately five decades of continuous studies and tests by multiple scientists, Howard Temin presented the concept of reverse transcription, making a big leap in knowledge and discoveries of retroviruses. By the 1970 s, Richard Nixon s failed attempt to find any retroviral agents that caused human 1 (Glossory of Cancer Terms, 2010)

3 cancer helped the biomedical research gain a large sum of money in order to proceed with the research. Just about 10 years later, the first pathogenic human virus retrovirus (human leukemia virus) was discovered. A mere two years later, human immunodeficiency virus (HIV) was discovered by Luc Montagnier. 2 Although the research and discoveries has become increasingly more sufficient, the discoveries of human leukemia virus and human immunodeficiency were the break through to retrovirus detections. Regarding the research and discoveries in the past, it is evident that although there is a great diversity between the types of retroviruses, all have a similar make up of the same eight proteins which are needed for the retrovirus to be sufficed. On the other hand, retroviruses may have more essential or non-essential proteins. The general eight proteins consist of the matrix, capsid, nucleocapsid, protease, reverse transcriptase, integrase, surface glycoprotein, and transmembrane protein. (The matrix, capsid, and nucleocapsid are all gag proteins while reverse transcriptase is a pol protein.) The matrix proteins line the envelope while the capsid proteins protect the core. Nucleocapsid proteins protect the genome and form the core. Protease proteins are essential for gag protein cleavage during maturation. Reverse transcriptase proteins reverse transcribes the RNA genome and intergrase proteins are encoded by the pol (reverse transcriptase) gene and are needed for integration of the provirus. Surface glycoproteins consist of being the outer envelope glycoprotein while being a major virus antigen. Lastly, transmembrane proteins are the inner component of the mature envelope glycoprotein. 3 Without all eight proteins, retroviruses will not be able to work properly thus fail to infect other host cells. 2 (Cann, 2009) 3 (Cann, 2009)

4 Also due to previous research, it is obvious each retrovirus must undergo a replication cycle in order to infect their host cell. Generally, a retrovirus uses reverse transcriptase to replicate in the host cell in order to produce DNA from its RNA genome. 4 The RNA genome is initially surrounded by a capsid containing core proteins and is thus surrounded by the outer layer, the lipid envelope which includes receptor binding proteins. It is these receptor binding proteins that originally link to the cell surface receptors of the host cell in order to begin the infection process. 5 After the first connection of the receptor binding proteins and the cell surface receptors, the virus nucleoprotein core is injected into the host cell. The virus nucleoprotein generally consists of gag-derived proteins (polyprotein), full length genome RNA, and reverse transcriptase protein. Once the nucleoprotein is completely injected into the cell, it accesses the intracellular DNA nucleotide triphosphate pools in order for the reverse transcriptase protein to start the creation of a double-stranded DNA copy of the genome of the virus. This step is necessary for the preparation of integration into the host cell chromosome. Upon the completion of the reverse transcriptase, the DNA is found a home by the viral enzyme integrase. After finding a home for the DNA, the integrase cuts the host DNA and sews the double-standard DNA (copied from the genome of the virus) into the host DNA thus allowing the virus to start a new round of replication. 6 Depending on the specific type or retrovirus, the complex process of infection and reproduction of the viron could move rather quickly or extremely slow. Moreover, this general notion of the replication cycle can vary due to the viron structure. The viron structure is determined depending on the retroviral class. Therefore, each specific retroviral class has a common viron shape or structure. For instance, A-type particles are non- 4 (The Retrovirus Life Cycle) 5 (Diagram of a Retrovirus, 2009) 6 (The Retrovirus Life Cycle)

5 enveloped, immature particles that are only visible inside cells. These particles are possibly noninfectious and believe to be the result of endogenous retrovirus-like genetic elements. Bearing in mind A-type particles may not be infectious there is no set virus that can be linked to it. Additionally, B-type particles are enveloped and are known to have a prominent surface protein spikes while C-type particles are similar to B-type although, C-type have a cone shaped-central core, barely visible spikes, and form at the surface of the cell at the site of budding. B-type particles generally linked with MMTV (mouse mammary tumor virus) while C-type cells are linked with more serious viruses such as HIV (human immunodeficiency virus) and HTLV (human T-lymphotrophic virus.) Lastly, D-type is also similar to B-type in every way though they have no spikes at all. D-type is also associated with MMTV. 7 When focusing on the specific retrovirus, human immunodeficiency virus, characteristics and ways of infection become more specified. This retrovirus is labeled lentivirus considering lentus in Latin means slow and HIV is a very gradual infectious disease. 8 Furthermore, HIV is an enveloped retrovirus which forms at the surface site of budding (C-type.) This envelope is also known as a lipid bilayer, which holds viral glycoproteins. It is these glycoproteins that connect to CD4 T-cell receptors, allowing the virus to fuse into the cell. After the virus fuses into the cell, the lipid membrane of the virus integrates into the membrane of the cell allowing the viral core to enter the host cell. While the viral core enters, RNA is allowed to enter the cytoplasm. Additionally, the enzymes carried by the viral particle aid in the viral replication. The viral enzymes convert the RNA into DNA thus allowing the protein, reverse transcriptase, to copy the RNA into cdna. While copying the RNA into cdna, errors are made thus leaving 7 (Cann, 2009) 8 (Levasseur)

6 mutations in the cdna. It is these mutations which allow HIV to evolve more quickly. Additionally, the viral RNA is destroyed due to ribonuclease H thus forcing the reverse transcriptase to create a double-stranded DNA. The double-stranded DNA thus enters the nucleus along with the protein integrase. Integrase enters the nucleus with the double-stranded DNA in order for it to cut the viral DNA into the host cells chromosomal DNA consequently making a provirus. After the provirus is created, transcription of DNA into RNA takes place. This viral RNA holds the code in order to produce capsid proteins as well as many others. The RNA also codes the envelope proteins which are formed in the endoplasmic reticulum. The envelope proteins must make their way through the Golgi thus arriving at the cell surface. All the viral components then come together at the cell membrane and detach from the host cell. This causes destruction of the helper T-cells and destroys the immune system. Noticeably, the general infection of a retrovirus is very similar to the way viral particles affect the human to synthesize HIV. It is small changes within the process that make the effect of HIV harmful and intense then other retroviruses, such as those that fit into the A-type category. 9 Retroviruses have been researched since the eighteenth century and are still being studied today. Although many theories and discoveries have made, we still lack knowledge on how to stop most retroviruses, such as HIV. Many retroviruses are more complex and have miniscule changes that separate them from other retroviruses. Therefore, scientists are able to label the retroviruses into categories due to their characteristics, shapes, and infectious actions. On the other hand, every retrovirus undergoes a similar replication cycle which replicates backwards (thus uses the protein reverse transcriptase.) Bearing in mind the replication cycles are so similar, all retroviruses carry the same eight proteins even though they may have more essential 9 (Life Cycle of HIV, A Retrovirus, 2006)

7 or non essential proteins as well. Although the differences between retroviruses, all are infectious particles which contained RNA rather than DNA as its genetic material thus all are an RNA virus.

8 Works Cited Cann, D. A. (2009, 8 April). Retrieved May 1,2010, from Microbiology Bites: Diagram of a Retrovirus. (2009). Retrieved May 1,2010, from Access Excellence at the National Health Museum Resouce Center: Glossory of Cancer Terms. (2010). Retrieved May 1, 2010, from The University of Texas MD Anderson Cancer Center: Levasseur, K. (n.d.). HIV is a Retrovirus. Retrieved May 2, 2010, from Human Imunnodeficiency Virus: Life Cycle of HIV, A Retrovirus. (2006). Retrieved May 3, 2010, from The Retrovirus Life Cycle. (n.d.). Retrieved May 1, 2010, from Stanford University:

VIRUSES. 1. Describe the structure of a virus by completing the following chart.

VIRUSES. 1. Describe the structure of a virus by completing the following chart. AP BIOLOGY MOLECULAR GENETICS ACTIVITY #3 NAME DATE HOUR VIRUSES 1. Describe the structure of a virus by completing the following chart. Viral Part Description of Part 2. Some viruses have an envelope