Editing Rubella virus

{{Short description|Species of virus}}
{{Use dmy dates|date=April 2017}}
{{Virusbox 
| name = Rubella virus
| image = Rubella virus TEM B82-0203 lores.jpg
| image_alt = Transmission electron micrograph of Rubella virus virions
| image_caption = [[Transmission electron micrograph]] of Rubella virus virions
| parent = Rubivirus
| species = Rubivirus rubellae
| synonyms = * Rubella virus
| synonyms_ref = <ref name=bennett >{{cite web |title=Create two new species and rename one species in genus ''Rubivirus'' (''Hepelivirales'': ''Matonaviridae'') |url=https://ictv.global/ictv/proposals/2020.011S.R.Rubivirus_nspp.zip |vauthors=Bennett AJ, Paskey AC, Ebinger A, Kuhn JH, Bishop-Lilly KA, Beer M, Goldberg TL |publisher=International Committee on Taxonomy of Viruses (ICTV) |language=en |format=docx |date=31 July 2020 |access-date=15 May 2021 |archive-date=21 December 2022 |archive-url=https://web.archive.org/web/20221221071302/https://ictv.global/ictv/proposals/2020.011S.R.Rubivirus_nspp.zip |url-status=live }}</ref>
}}

'''Rubella virus''' ('''RuV''') is the [[Pathogen|pathogenic agent]] of the disease [[rubella]], transmitted only between humans via the respiratory route, and is the main cause of [[congenital rubella syndrome]] when infection occurs during the first weeks of [[pregnancy]].

Rubella virus, scientific name ''Rubivirus rubellae'', is a member of the [[genus]] ''[[Rubivirus]]'' and belongs to the [[Family (biology)|family]] of ''Matonaviridae'', whose members commonly have a [[genome]] of single-stranded [[RNA]] of [[Sense (molecular biology)|positive polarity]] which is enclosed by an [[Icosahedron|icosahedral]] [[capsid]].

{{As of| 1999}} the molecular basis for the causation of [[congenital rubella syndrome]] was not yet completely clear, but ''[[in vitro]]'' studies with cell lines showed that rubella virus has an [[apoptosis|apoptotic]] effect on certain cell types. There is evidence for a [[p53]]-dependent mechanism.<ref name="pmid10364491">{{cite journal  |vauthors=Megyeri K, Berencsi K, Halazonetis TD, etal |title=Involvement of a p53-dependent pathway in rubella virus-induced apoptosis |journal=Virology |volume=259 |issue=1 |pages=74–84 |date=June 1999 |pmid=10364491 |doi=10.1006/viro.1999.9757 |doi-access=free }}</ref>

==Taxonomy==
Rubella virus (''Rubivirus rubellae'') is assigned to the ''Rubivirus'' genus.<ref name=bennett />

===''Matonaviridae'' family===
Until 2018, Rubiviruses were classified as part of the family ''[[Togaviridae]]'', but have since been changed to be the sole genus of the family ''Matonaviridae''. This family is named after George de Maton, who in 1814 first distinguished rubella from [[measles]] and [[scarlet fever]].<ref name="ICTVProposal">{{cite web|vauthors=Chen R, Mukhopadhyay S, Merits A, Bolling B, Nasar F, Coffey LL, Powers A, Weaver S, Smith D, Simmonds P, Siddell S|title=Create a new family ''Matonaviridae'' to include the genus ''Rubivirus'', removed from the family ''Togaviridae''|url=https://ictv.global/ictv/proposals/2018.013S.A.v3.Matonaviridae.zip|format=docx|website=ictv.global|publisher=International Committee on Taxonomy of Viruses|date=June 2018|access-date=21 January 2025|language=en}}</ref> The change was made by the [[International Committee on the Taxonomy of Viruses]] (ICTV), the central governing body for [[Virus classification|viral classification]]. ''Matonaviridae'' remains part of the realm that it was already in as ''Togaviridae'', ''[[Riboviria]]'', because of its RNA genome and [[RNA-dependent RNA polymerase|RNA dependent RNA polymerase]]''.''<ref name="ICTVProposal" />

===Other rubiviruses===
In 2020, [[Ruhugu virus]] and [[Rustrela virus]] joined  Rubella virus as second and third of only three members of the genus ''Rubivirus''.<ref name="nature">{{Cite journal |last1=Bennett |first1=Andrew J. |last2=Paskey |first2=Adrian C. |last3=Ebinger |first3=Arnt |last4=Pfaff |first4=Florian |last5=Priemer |first5=Grit |last6=Höper |first6=Dirk |last7=Breithaupt |first7=Angele |last8=Heuser |first8=Elisa |last9=Ulrich |first9=Rainer G. |last10=Kuhn |first10=Jens H. |last11=Bishop-Lilly |first11=Kimberly A. |date=2020-10-07 |title=Relatives of rubella virus in diverse mammals |url= |journal=Nature |language=en |pages=1–5 |doi=10.1038/s41586-020-2812-9 |pmid=33029010 |issn=1476-4687|pmc=7572621 }}</ref> Neither of them are known to infect people.<ref name="science">{{Cite journal|last1=Gibbons|first1=Ann|date=2020-10-07|title=Newly discovered viruses suggest 'German measles' jumped from animals to humans|url=https://www.science.org/content/article/newly-discovered-viruses-suggest-rubella-jumped-animals-humans|language=en|doi=10.1126/science.abf1520|journal=science|access-date=30 June 2022|archive-date=8 December 2022|archive-url=https://web.archive.org/web/20221208104617/https://www.science.org/content/article/newly-discovered-viruses-suggest-rubella-jumped-animals-humans|url-status=live|url-access=subscription}}</ref>

== Morphology ==
While alphavirus virions are spherical and contain an [[icosahedral]] [[nucleocapsid]], RuV virions are pleiomorphic and do not contain icosahedral nucleocapsids.<ref name="ICTVProposal" />

=== Phylogeny ===
ICTV analyzed the sequence of RuV and compared its [[phylogeny]] to that of togaviruses. They concluded:<blockquote>Phylogenetic analysis of the RNA-dependent RNA polymerase of alphaviruses, rubella virus and other positive-sense RNA viruses shows the two genera within the ''Togaviridae'' are not monophyletic. In particular, rubella virus groups more closely with members of the families ''[[Benyviridae]]'', ''[[Hepeviridae]]'' and ''[[Alphatetraviridae]]'', along with several unclassified viruses, than it does with members of the family ''Togaviridae'' belonging to the genus ''Alphavirus''.<ref name="ICTVProposal" /> </blockquote>

==Structure==
The spherical virus particles ([[virion]]s) of Matonaviridae have a diameter of 50 to 70&nbsp;nm and are covered by a lipid membrane ([[viral envelope]]), derived from the host cell membrane. There are prominent "spikes" (projections) of 6&nbsp;nm  composed of the viral envelope proteins E1 and E2 embedded in the membrane.<ref name="pmid1212096">{{cite journal |vauthors=Bardeletti G, Kessler N, Aymard-Henry M |title=Morphology, biochemical analysis and neuraminidase activity of rubella virus |journal=Arch. Virol. |volume=49 |issue=2–3 |pages=175–86 |year=1975 |pmid=1212096 |doi= 10.1007/BF01317536}}</ref>

The E1 glycoprotein is considered immunodominant in the humoral response induced against the structural proteins and contains both neutralizing and hemagglutinating determinants.
{| class="wikitable sortable" style="text-align:center"
|-
! Genus !! Structure || Symmetry !! Capsid !! Genomic arrangement !! Genomic segmentation
|-
|''Rubivirus''||Icosahedral||T=4||Enveloped||Linear||Monopartite
|}<ref name=ViralZone>{{cite web|title=Viral Zone|url=http://viralzone.expasy.org/all_by_species/626.html|publisher=ExPASy|access-date=15 June 2015|archive-date=24 June 2015|archive-url=https://web.archive.org/web/20150624181523/http://viralzone.expasy.org/all_by_species/626.html|url-status=live}}</ref>

=== Capsid protein ===
Inside the lipid envelope is a capsid of 40&nbsp;nm in diameter. The capsid protein (CP) has different functions.<ref name="pmid15047844">{{cite journal |vauthors=Chen MH, Icenogle JP |title=Rubella virus capsid protein modulates viral genome replication and virus infectivity |journal=Journal of Virology |volume=78 |issue=8 |pages=4314–22 |date=April 2004 |pmid=15047844 |pmc=374250 |doi= 10.1128/jvi.78.8.4314-4322.2004|url=}}</ref> Its main tasks are the formation of homo[[oligomere]]s to form the capsid, and the binding of the genomic RNA. Further is it responsible for the aggregation of RNA in the capsid, it interacts with the membrane proteins E1 and E2 and binds the human host-protein p32 which is important for replication of the virus in the host.<ref name="pmid16051872">{{cite journal |vauthors=Beatch MD, Everitt JC, Law LJ, Hobman TC |title=Interactions between rubella virus capsid and host protein p32 are important for virus replication |journal=J. Virol. |volume=79 |issue=16 |pages=10807–20 |date=August 2005 |pmid=16051872 |pmc=1182682 |doi=10.1128/JVI.79.16.10807-10820.2005 }}</ref>

As opposed to alphaviruses the capsid does not undergo autoproteolysis, rather is it cut off from the rest of the polyprotein by the signal-[[peptidase]]. Production of the capsid happens at the surface of intracellular membranes simultaneously with the budding of the virus.<ref name="pmid10823864">{{cite journal |vauthors=Beatch MD, Hobman TC |title=Rubella virus capsid associates with host cell protein p32 and localizes to mitochondria |journal=J. Virol. |volume=74 |issue=12 |pages=5569–76 |date=June 2000 |pmid=10823864 |pmc=112044 |doi= 10.1128/JVI.74.12.5569-5576.2000|url=}}</ref>
==Genome==
The [[Positive-strand RNA virus|positive-strand]] RNA genome has 9,762 [[nucleotides]] and encodes 2 nonstructural [[polypeptides]] (p150 and p90) within its 5′-terminal two-thirds and 3 structural polypeptides (C, E2, and E1) within its 3′-terminal one-third.<ref name="pmid2353453">{{cite journal |vauthors=Dominguez G, Wang CY, Frey TK |title=Sequence of the genome RNA of rubella virus: evidence for genetic rearrangement during togavirus evolution |journal=Virology |volume=177 |issue=1 |pages=225–38 |date=July 1990 |pmid=2353453 |doi= 10.1016/0042-6822(90)90476-8|pmc=7131718 }}</ref> 
Both envelope proteins E1 and E2 are [[glycosylation|glycosylated]].

There are three sites that are highly conserved in Matonaviruses: a stem-and-loop structure at the 5' end of the genome, a 51-nucleotide conserved sequence near the 5' end of the genome and a 20-nucleotide conserved sequence at the subgenomic RNA start site. Homologous sequences are present in the rubella genome.<ref name="pmid2353453"/>

The genome encodes several [[non-coding RNA]] structures; among them is the [[rubella virus 3' cis-acting element]], which contains multiple [[stem-loop]]s, one of which has been found to be essential for viral replication.<ref name="Che99">{{cite journal | last = Chen | first = MH |author2=Frey TK  | year = 1999 | title = Mutagenic analysis of the 3' cis-acting elements of the rubella virus genome | journal = J Virol | volume = 73 | pages = 3386&ndash;3403 | pmid = 10074193 | issue = 4 | pmc = 104103}}</ref>

The only significant region of homology between rubella and the [[alphavirus]]es is located at the NH2 terminus of non structural protein 3. This sequence has [[helicase]] and [[replicase]] activity. In the rubella genome these occur in the opposite orientation to that found in the alphaviruses indicating that a genome rearrangement has occurred.

The genome has the highest [[G+C]] content of any currently known single stranded RNA virus (~70%).<ref name=Zhou2012>Zhou Y, Chen X, Ushijima H, Frey TK (2012) Analysis of base and codon usage by rubella virus. Arch Virol</ref> Despite this high GC content its codon use is similar to that of its human host.

== Replication ==
The viruses attach to the cell surface via specific receptors and are taken up by an [[endosome]] being formed. At the neutral [[pH]] outside of the cell the E2 envelope protein covers the E1 protein. The dropping pH inside the endosome frees the outer domain of E1 and causes the fusion of the viral envelope with the endosomal membrane. Thus, the capsid reaches the [[cytosol]], decays and releases the genome

The +ssRNA ([[Sense (molecular biology)|positive]], single-stranded [[RNA]]) at first only acts as a template for the translation of the non-structural proteins, which are synthesized as a large [[polyprotein]] and are then cut into single proteins. The sequences for the structural proteins are first replicated by the viral [[RNA polymerase]] (Replicase) via a complementary &minus;ssRNA as a template and translated as a separate short mRNA. This short subgenomic RNA is additionally packed in a virion.<ref name="urlTogaviridae- Classification and Taxonomy">{{cite web |url=http://www.stanford.edu/group/virus/toga/class.html |title=Togaviridae- Classification and Taxonomy |access-date=10 May 2009 |archive-date=5 August 2012 |archive-url=https://web.archive.org/web/20120805131040/http://www.stanford.edu/group/virus/toga/class.html |url-status=live }}</ref>

Translation of the structural proteins produces a large polypeptide (110 [[Dalton (unit)|kDa]]). This is then [[proteolysis|endoproteolytically]] cut into E1, E2 and the capsid protein. E1 and E2 are type I [[transmembrane protein]]s which are transported into the [[endoplasmatic reticulum]] (ER) with the help of an [[amino terminus|N-terminal]] signal sequence. From the ER the heterodimeric E1·E2-complex reaches the [[Golgi apparatus]], where the budding of new [[virion]]s occurs (unlike alpha viruses, where budding occurs at the plasma membrane.
The capsid proteins on the other hand stay in the cytoplasm and interact with the genomic RNA, together forming the capsid.<ref name="pmid10196241">{{cite journal |vauthors=Garbutt M, Law LM, Chan H, Hobman TC |title=Role of rubella virus glycoprotein domains in assembly of virus-like particles |journal=J. Virol. |volume=73 |issue=5 |pages=3524–33 |date=May 1999 |pmid=10196241 |pmc=104124 |url=}}</ref>
{| class="wikitable sortable" style="text-align:center"
|-
! Genus !! Host details !! Tissue tropism !! Entry details !! Release details !! Replication site !! Assembly site !! Transmission
|-
|''Rubivirus''||Humans||None||Clathrin-mediated endocytosis||Secretion||Cytoplasm||Cytoplasm||Aerosol
|}<ref name=ViralZone />

== Transmission ==
RuV is transmitted via respiration between humans.<ref name="ICTVProposal" />

==Epidemiology==
On the basis of differences in the sequence of the E1 protein, two genotypes have been described which differ by 8 - 10%. These have been subdivided into 13 recognised genotypes - 1a, 1B, 1C, 1D, 1E, 1F, 1G, 1h, 1i, 1j, 2A, 2B and 2C.

For typing, the WHO recommends a minimum window that includes nucleotides 8731 to 9469.<ref name=rubellaWHO>{{cite journal
 | year = 2005
 | title = Standardization of the nomenclature for genetic characteristics of wild-type rubella viruses
 | journal = Wkly Epidemiol Rec
 | volume = 80
 | issue = 14
 | pages = 126–132
 | pmid = 15850226
 | url =https://www.who.int/immunization_monitoring/Rubella_nomemclature_report.pdf
| archive-url =https://web.archive.org/web/20090518152931/http://www.who.int/immunization_monitoring/Rubella_nomemclature_report.pdf
| url-status =dead
| archive-date =18 May 2009
}}</ref>

Genotypes 1a, 1E, 1F, 2A and 2B have been isolated in [[China]].

Genotype 1j has only been isolated from [[Japan]] and the [[Philippines]].

Genotype 1E is found in [[Africa]], the [[Americas]], [[Asia]] and [[Europe]].

Genotype 1G has been isolated in [[Belarus]], [[Côte d'Ivoire]] and [[Uganda]].

Genotype 1C is endemic only in Central and South America.

Genotype 2B has been isolated in [[South Africa]].

Genotype 2C has been isolated in [[Russia]].

== Literature ==
*David M. Knipe, Peter M. Howley et al. (eds.): ''Fields Virology'' 4. Auflage, Philadelphia 2001
*C.M. Fauquet, M.A. Mayo et al.: ''Eighth Report of the International Committee on Taxonomy of Viruses'', London San Diego 2005

== References ==
{{Reflist|2}}

==External links==
* [http://www.expasy.org/viralzone/all_by_species/626.html '''Viralzone''': Rubivirus]

{{Baltimore classification}}
{{Viral cutaneous conditions}}

{{Taxonbar|from=Q701609}}

[[Category:Rubella]]
[[Category:Rubivirus]]
[[Category:Togaviruses]]