Editing Retrovirus (section)

== Structure ==
[[Virion]]s, viruses in the form of independent particles of retroviruses, consist of enveloped particles about 100&nbsp;[[Nanometre|nm]] in diameter. The outer lipid envelope consists of glycoprotein.<ref>{{Cite book |last1=Coffin |first1=John M. |url=https://www.ncbi.nlm.nih.gov/books/NBK19382/ |title=The Place of Retroviruses in Biology |last2=Hughes |first2=Stephen H. |last3=Varmus |first3=Harold E. |date=1997 |publisher=Cold Spring Harbor Laboratory Press |language=en}}</ref> The virions also contain two identical single-stranded [[RNA]] molecules 7–10 [[base pair#Length measurements|kilobases]] in length. The two molecules are present as a dimer, formed by base pairing between complementary sequences. Interaction sites between the two RNA molecules have been identified as a "[[kissing stem-loop]]".<ref name=":1">{{Cite book |last1=Carter |first1=John B |title=Virology: principles and applications |last2=Saunders |first2=Venetia A. |date=2007 |publisher=John Wiley & Sons |isbn=978-0-470-02386-0 |edition=1st |location=Chichester, England |pages=191 |oclc=124160564 |name-list-style=vanc}}</ref> Although virions of different retroviruses do not have the same [[morphology (biology)|morphology]] or biology, all the virion components are very similar.<ref name = she>{{Cite book |first= John M. |last=Coffin |editor-first = Jay A. |editor-last =Levy |name-list-style = vanc |title = The Retroviridae |edition = 1st | publisher = Plenum |location = New York |year = 1992 |chapter = Structure and Classification of Retroviruses |pages = 20 |isbn =978-0-306-44074-8 |volume =1 }}</ref>

The main virion components are:
* [[Viral envelope|Envelope]]: composed of lipids (obtained from the host [[plasma membrane]] during the [[budding]] process) as well as glycoprotein encoded by the [[Env (gene)|env gene]]. The retroviral envelope serves three distinct functions: protection from the extracellular environment via the [[lipid bilayer]], enabling the retrovirus to enter/exit host cells through [[endosome|endosomal]] [[membrane vesicle trafficking|membrane trafficking]], and the ability to directly enter cells by fusing with their membranes.
* [[RNA]]: consists of a [[dimer (chemistry)|dimer]] RNA. It has a cap at the [[Directionality (molecular biology)|5']] end and a poly(A) tail at the 3' end. Genomic RNA (gRNA) is produced as a result of host RNA polymerase II (Pol II) activity and by adding a 5' methyl cap and a 3' poly-A tail is processed as a host mRNA.<ref name=":0">{{Citation |last1=Painter |first1=Mark M. |title=HIV and Retroviruses |date=2019-01-01 |url=http://www.sciencedirect.com/science/article/pii/B9780128012383662025 |encyclopedia=Encyclopedia of Microbiology (Fourth Edition) |pages=613–628 |editor-last=Schmidt |editor-first=Thomas M. |publisher=Academic Press |language=en |doi=10.1016/b978-0-12-801238-3.66202-5 |isbn=978-0-12-811737-8 |access-date=2020-05-03 |last2=Collins |first2=Kathleen L.|s2cid=188750910 }}</ref> The RNA genome also has terminal noncoding regions, which are important in replication, and internal regions that encode virion proteins for [[gene expression]]. The 5' end includes four regions, which are R, U5, PBS, and L. The R region is a short repeated sequence at each end of the genome used during the [[reverse transcription]] to ensure correct end-to-end transfer in the growing chain. U5, on the other hand, is a short unique sequence between R and PBS. PBS (primer binding site) consists of 18 bases complementary to 3' end of tRNA primer. L region is an untranslated leader region that gives the signal for packaging of the genome RNA. The 3' end includes three regions, which are PPT (polypurine tract), U3, and R. The PPT is a primer for plus-strand DNA synthesis during [[reverse transcription]]. U3 is a sequence between PPT and R, which serves as a signal that the provirus can use in [[Transcription (genetics)|transcription]]. R is the terminal repeated sequence at 3' end.
* [[Protein]]s: consisting of gag proteins, [[protease]] (PR), pol proteins, and env proteins.
** [[Group-specific antigen]] (gag) proteins are major components of the viral [[capsid]], which are about 2000–4000 copies per virion. Gag possesses two nucleic acid binding domains, including matrix (MA) and nucleocapsid (NC). Specifically recognizing, binding, and packaging the retroviral genomic RNA into assembling virions is one of the important functions of Gag protein. Gag interactions with cellular RNAs also regulate aspects of assembly.<ref>{{cite journal |vauthors = Olson ED, Musier-Forsyth K |title = Retroviral Gag protein-RNA interactions: Implications for specific genomic RNA packaging and virion assembly |journal = Seminars in Cell & Developmental Biology |volume = 86 |pages = 129–139 |date = February 2019 |pmid = 29580971 |doi = 10.1016/j.semcdb.2018.03.015 |url= |series = SI: Human dendritic cells |pmc = 6167211}}</ref> The expression of ''gag'' alone gives rise to assembly of immature virus-like particles that bud from the plasma membrane. In all retroviruses the Gag protein is the precursor to the internal structural protein.<ref>{{Cite book |last1=Coffin |first1=John M. |last2=Hughes |first2=Stephen H. |last3=Varmus |first3=Harold E. |name-list-style = vanc |url=https://www.ncbi.nlm.nih.gov/books/NBK19464/|title=Virion Proteins |date=1997 |publisher=Cold Spring Harbor Laboratory Press |language=en |isbn= 978-0-87969-571-2 }}</ref>
** [[Retroviral aspartyl protease|Protease]] (pro) is expressed differently in different viruses. It functions in proteolytic cleavages during virion maturation to make mature gag and pol proteins. Retroviral Gag proteins are responsible for coordinating many aspects of virion assembly.
** [[Pol proteins]] are responsible for synthesis of viral DNA and integration into host DNA after infection.
** [[Env proteins]] play a role in association and entry of virions into the host cell.<ref name = se>{{harvnb|Coffin|1992|pp=26–34}}</ref> Possessing a functional copy of an [[Env (gene)|env gene]] is what makes retroviruses distinct from [[retroelements]].<ref>{{cite journal |vauthors = Kim FJ, Battini JL, Manel N, Sitbon M |title = Emergence of vertebrate retroviruses and envelope capture |journal = Virology |volume = 318 |issue = 1|pages = 183–91 |date = January 2004 |pmid = 14972546 |doi = 10.1016/j.virol.2003.09.026 |doi-access = free }}</ref> The ability of the retrovirus to bind to its target host cell using specific cell-surface receptors is given by the surface component (SU) of the Env protein, while the ability of the retrovirus to enter the cell via [[lipid bilayer fusion|membrane fusion]] is imparted by the membrane-anchored trans-membrane component (TM). Thus it is the Env protein that enables the retrovirus to be infectious.
** Several protein species are associated with the RNA in the retrovirus virion. Nucleocapsid (NC) protein is the most abundant protein, which coats the RNA; while other proteins, present in much smaller amounts and have enzyme activities. Some enzyme activities that are present in the retrovirus virion includes RNA-dependent DNA polymerase (reverse transcriptase; RT), DNA-dependent DNA polymerase, Ribonuclease H (RNase H) Integrase and Protease.<ref name="John Wiley & Sons">{{Cite book |first1 = John B |last1 = Carter |first2 = Venetia A |last2 = Saunders |name-list-style = vanc |title=Virology : principles and applications |date=2007 |publisher=John Wiley & Sons |isbn=978-0-470-02386-0 |location=Chichester, England |oclc=124160564}}</ref> The retroviral RNases H encoded by all retroviruses, including HIV have been demonstrated to show three different modes of cleavage: internal, DNA 3′ end-directed, and RNA 5′ end-directed. All three modes of cleavage constitute roles in reverse transcription. Therefore, The RNase H activity is essential in several aspects of reverse transcription. The use of an RNase H activity during retroviral replication displays a unique strategy to copy a single-stranded RNA genome into a double-stranded DNA, since the minus-strand DNA are complementary and make base pairing to retrovirus genome in the first cycle of DNA synthesis.<ref>{{cite journal |vauthors = Champoux JJ, Schultz SJ |title = RNase H Activity: Structure, Specificity, and Function in Reverse Transcription |journal = The FEBS Journal |volume = 134 |issue = 1–2 |pages = 86–103 |date = Jun 2009  |pmid = 18261820 |pmc = 2464458 |doi = 10.1016/j.virusres.2007.12.007 }}</ref> The RNase H ribonuclease activity is also required in the retroviral life cycle, since it generates and removes primers essential by the Reverse Transcriptase (RT) for the initiation of DNA synthesis. Retroviruses that are lacking RNase H activity are noninfectious.<ref>{{cite book |vauthors = Moelling K, Broecker F, Kerrigan JE |title = Human Retroviruses |chapter = RNase H: specificity, mechanisms of action, and antiviral target |series = Methods in Molecular Biology |volume = 1087 |pages = 71–84 |date = 2014 |pmid = 24158815 |doi = 10.1007/978-1-62703-670-2_7 |isbn = 978-1-62703-669-6 }}</ref>

[[File:Prototypical retrovirus genomic organization.svg|thumb|upright=1.25|The genomic and subgenomic organization of a prototypical retrovirus. Abbreviations are explained in the file description.<ref name="pmid26800882">{{cite journal |vauthors = Vargiu L, Rodriguez-Tomé P, Sperber GO, Cadeddu M, Grandi N, Blikstad V, Tramontano E, Blomberg J |display-authors = 6 |title = Classification and characterization of human endogenous retroviruses; mosaic forms are common |journal = Retrovirology |volume = 13 |pages = 7 |date = January 2016 |pmid = 26800882 |pmc = 4724089 |doi = 10.1186/s12977-015-0232-y |doi-access = free}}</ref>]]

=== Genomic structure ===
The retroviral genome is packaged as viral particles. These viral particles are dimers of single-stranded, positive-sense, linear RNA molecules.<ref name=":0" />

Retroviruses (and [[Ortervirales|orterviruses]] in general) follow a layout of 5'–''gag''–''pro''–''pol''–''env''–3' in the RNA genome. ''gag'' and ''pol'' encode polyproteins, each managing the capsid and replication. The ''pol'' region encodes enzymes necessary for viral replication, such as reverse transcriptase, protease and integrase.<ref>Peters, P. J., Marston, B. J., Weidle, P. J., & Brooks, J. T. (2013). Human Immunodeficiency Virus Infection. Hunter's Tropical Medicine and Emerging Infectious Disease, 217–247. doi:10.1016/b978-1-4160-4390-4.00027-8</ref> Depending on the virus, the genes may overlap or fuse into larger polyprotein chains. Some viruses contain additional genes. The lentivirus genus, the spumavirus genus, the HTLV / bovine leukemia virus (BLV) genus, and a newly introduced fish virus genus are retroviruses classified as complex. These viruses have genes called accessory genes, in addition to gag, pro, pol and env genes. Accessory genes are located between pol and env, downstream from the env, including the U3 region of LTR, or in the env and overlapping portions. While accessory genes have auxiliary roles, they also coordinate and regulate viral gene expression.
In addition, some retroviruses may carry genes called oncogenes or onc genes from another class. Retroviruses with these genes (also called transforming viruses) are known for their ability to quickly cause tumors in animals and transform cells in culture into an oncogenic state.<ref>{{cite book |last1=Coffin |first1=John M. |last2=Hughes |first2=Stephen H. |last3=Varmus |first3=Harold E. | name-list-style = vanc |title=Retroviruses |date=1997 |publisher=Cold Spring Harbor Laboratory Press |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK19370/ |language=en |chapter=Genetic Organization |isbn= 978-0-87969-571-2 }}</ref>

The polyproteins are cleaved into smaller proteins each with their own function. The nucleotides encoding them are known as ''subgenes''.<ref name="pmid26800882"/>