Measles virus

{{Main|Measles}}

The virus causes measles, a highly contagious disease transmitted by respiratory aerosols that triggers a temporary but severe immunosuppression. Symptoms include fever, cough, runny nose, inflamed eyes and a generalized, maculopapular, erythematous rash and a pathognomonic Koplik spot seen on buccal mucosa opposite to lower 1st and 2nd molars. The virus is spread by coughing and sneezing via close personal contact or direct contact with secretions.{{Cite web |last=CDC |date=2020-11-05 |title=Measles is Easily Transmitted |url=https://www.cdc.gov/measles/transmission.html |access-date=2023-12-28 |website=Centers for Disease Control and Prevention |language=en-us}}

File:Receptors MV.tif

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The measles virus has two envelope glycoproteins on the viral surface – hemagglutinin (H) and membrane fusion protein (F). These proteins are responsible for host cell binding and invasion. The H protein mediates receptor attachment and the F protein causes fusion of viral envelope and cellular membrane. Additionally, the F protein can cause infected cells to directly fuse with neighboring uninfected cells forming syncytia. Three receptors for the H protein have been identified to date: complement regulatory molecule CD46, the signaling lymphocyte activation molecule (SLAMF1) and the cell adhesion molecule Nectin-4.{{cite journal |vauthors=Lu G, Gao GF, Yan J |date=2013 |title=The receptors and entry of measles virus: a review |journal=Sheng Wu Gong Cheng Xue Bao |volume=29 |issue=1 |pages=1–9| language=zh |pmid=23631113 }} For wild type and vaccine strains, extracellular domains of CD150 (SLAM or SLAMF1){{Cite journal|last1=Tatsuo|first1=Hironobu|last2=Ono|first2=Nobuyuki|last3=Tanaka|first3=Kotaro|last4=Yanagi|first4=Yusuke|date=24 August 2000|title=SLAM (CDw150) is a cellular receptor for measles virus|journal=Nature|volume=406|issue=6798|pages=893–897|doi=10.1038/35022579|pmid=10972291|bibcode=2000Natur.406..893T|s2cid=4409405|issn=0028-0836}}{{Cite journal|last1=Tatsuo|first1=Hironobu|last2=Yanagi|first2=Yusuke|date=March 2002|title=The Morbillivirus Receptor SLAM (CD150)|journal=Microbiology and Immunology|volume=46|issue=3|pages=135–142|doi=10.1111/j.1348-0421.2002.tb02678.x|pmid=12008921|s2cid=30651799|issn=0385-5600|doi-access=free}} and/or of nectin-4 (also called Poliovirus-Receptor-Like 4 (PVRL4)){{Cite book|last=Mühlebach, Michael D Mateo, Mathieu Sinn, Patrick L Prüfer, Steffen Uhlig, Katharina M Leonard, Vincent H J Navaratnarajah, Chanakha K Frenzke, Marie Wong, Xiao X Sawatsky, Bevan Ramachandran, Shyam Mccray Jr, Paul B Cichutek, Klaus Von Messling, Veronika Lopez, Marc Cattaneo, Roberto|title=Adherens junction protein nectin-4 is the epithelial receptor for measles virus.|oclc=806252697}}{{Cite journal|last1=Noyce|first1=Ryan S.|last2=Richardson|first2=Christopher D.|date=20 June 2012|title=Nectin 4 is the epithelial cell receptor for measles virus|journal=Trends in Microbiology|volume=20|issue=9|pages=429–439|doi=10.1016/j.tim.2012.05.006|pmid=22721863|issn=0966-842X}} mainly work as cell entry receptors. A minor fraction of wild type virus strains and all modern vaccine strains derived from the Edmonston strain also use CD46.{{Cite journal|last1=Erlenhöfer|first1=Christian|last2=Duprex|first2=W. Paul|author-link2=William Paul Duprex|last3=Rima|first3=Bert K.|last4=ter Meulen|first4=Volker|last5=Schneider-Schaulies|first5=Jürgen|date=2002-06-01|title=Analysis of receptor (CD46, CD150) usage by measles virus|journal=Journal of General Virology|volume=83|issue=6|pages=1431–1436|doi=10.1099/0022-1317-83-6-1431|pmid=12029158|issn=0022-1317|doi-access=free}}{{Cite journal|last1=Lin|first1=Liang-Tzung|last2=Richardson|first2=Christopher|date=2016-09-20|title=The Host Cell Receptors for Measles Virus and Their Interaction with the Viral Hemagglutinin (H) Protein|journal=Viruses|volume=8|issue=9|pages=250|doi=10.3390/v8090250|pmid=27657109|pmc=5035964|issn=1999-4915|doi-access=free}}

Once the virus has entered a host cell, its strand of negative sense ssRNA is used as a template to create a positive sense copy using the RNA-dependent RNA polymerase that's included in the virion. Then this copy is used to create a new negative copy, and so on, to create many copies of the ssRNA. The positive sense ssRNA is then mass translated by host ribosomes, producing all viral proteins. The viruses are then assembled from their proteins and negative sense ssRNA, and the cell will lyse, discharging the new viral particles and restarting the cycle.{{Cite journal|last1=Jiang|first1=Yanliang|last2=Qin|first2=Yali|last3=Chen|first3=Mingzhou|date=2016-11-16|title=Host–Pathogen Interactions in Measles Virus Replication and Anti-Viral Immunity|journal=Viruses|volume=8|issue=11|pages=308|doi=10.3390/v8110308|issn=1999-4915|pmc=5127022|pmid=27854326|doi-access=free}}

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The RNA genome of the virus codes 6 main proteins Nucleoprotein (N), Phosphoprotein (P), Matrix protein (M), Fusion protein (F), Hemagglutinin (H), and Large Protein (L), which represents RNA dependent RNA polymerase (RdRp). The viral genome also codes two non-structural proteins C and V. These non-structural proteins are innate immunity antagonists; they help the virus to escape host immune response. Inside the virion genomic RNA is forming complex with N, L and P proteins. N, P and M proteins regulate RNA synthesis by RdRp. The virus is enveloped by a lipid membrane and glycoproteins H and F are virion surface proteins that are associated with this lipid membrane.{{cn|date=August 2022}}

File:231-Measles-virus-proteins.tif

{{main|Measles#History}}

The measles virus evolved from the now eradicated rinderpest virus which infected cattle. Sequence analysis has suggested that the two viruses most probably diverged in the 11th and 12th centuries, though the periods as early as the 5th century fall within the 95% confidence interval of these calculations.{{cite journal |vauthors=Furuse Y, Suzuki A, Oshitani H |title=Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries |journal=Virol. J. |volume=7 |pages=52 |year=2010 |pmid=20202190 |pmc=2838858 |doi=10.1186/1743-422X-7-52 |doi-access=free }}

Other analysis has suggested that the divergence may be even older because of the technique's tendency to underestimate ages when strong purifying selection is in action.{{Cite journal | last1 = Wertheim | first1 = J. O. | last2 = Kosakovsky Pond | first2 = S. L. | doi = 10.1093/molbev/msr170 | title = Purifying Selection Can Obscure the Ancient Age of Viral Lineages | journal = Molecular Biology and Evolution | volume = 28 | issue = 12 | pages = 3355–65 | year = 2011 | pmid = 21705379| pmc =3247791 }} There is some linguistic evidence for an earlier origin within the seventh century.{{cite book |author=Griffin DE |chapter=Measles Virus |editor1=Martin, Malcolm A. |editor2=Knipe, David M. |editor3=Fields, Bernard N. |editor4=Howley, Peter M. |editor5=Griffin, Diane |editor6=Lamb, Robert |title=Fields' virology |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |year=2007 |isbn=978-0-7817-6060-7 |edition=5th}}{{cite book |last=McNeil |first=W. |title=Plagues and Peoples |location=New York |publisher=Anchor Press/Doubleday |year=1976 |isbn=978-0-385-11256-7 |url-access=registration |url=https://archive.org/details/plaguespeoples00will }} The current epidemic strain evolved at the beginning of the 20th century—most probably between 1908 and 1943.{{cite journal |vauthors=Pomeroy LW, Bjørnstad ON, Holmes EC |title=The evolutionary and epidemiological dynamics of the paramyxoviridae |journal=J. Mol. Evol. |volume=66 |issue=2 |pages=98–106 |date=February 2008 |pmid=18217182 |doi=10.1007/s00239-007-9040-x |pmc=3334863|bibcode=2008JMolE..66...98P }}

The measles virus genome is typically 15,894 nucleotides long and encodes eight proteins.{{cite journal |last1=Phan |first1=MVT |last2=Schapendonk |first2=CME |last3=Oude Munnink |first3=BB |last4=Koopmans |first4=MPG |last5=de Swart |first5=RL |last6=Cotten |first6=M |title=Complete Genome Sequences of Six Measles Virus Strains. |journal=Genome Announcements |date=29 March 2018 |volume=6 |issue=13 |doi=10.1128/genomeA.00184-18 |pmid=29599155 |pmc=5876482 }} The WHO currently recognises 8 clades of measles (A–H). Subtypes are designed with numerals—A1, D2 etc. Currently, 23 subtypes are recognised. The 450 nucleotides that code for the C‐terminal 150 amino acids of N are the minimum amount of sequence data required for genotyping a measles virus isolate. The genotyping scheme was introduced in 1998 and extended in 2002 and 2003.{{cn|date=August 2022}}

Despite the variety of measles genotypes, there is only one measles serotype. Antibodies to measles bind to the hemagglutinin protein. Thus, antibodies against one genotype (such as the vaccine strain) protect against all other genotypes.{{cite web |title=Measles |date=11 March 2013 |work=Biologicals — Vaccine Standardization |publisher=World Health Organization |url=https://www.who.int/biologicals/vaccines/measles/en/|archive-url=https://web.archive.org/web/20140501133047/http://www.who.int/biologicals/vaccines/measles/en/|url-status=dead|archive-date=1 May 2014}}

The major genotypes differ between countries and the status of measles circulation within that country or region. Endemic transmission of measles virus was interrupted in the United States and Australia by 2000 and the Americas by 2002.{{cite web|url=http://www.paho.org/hq/index.php?option=com_content&view=article&id=9318%3A2014-no-endemic-transmission-measles-americas-since-2002&catid=1443%3Aweb-bulletins&Itemid=135&lang=en|title=No endemic transmission of measles in the Americas since 2002|publisher=Pan American Health Organization|date=14 February 2017|access-date=11 September 2017}}

In the early stages of infection, the measles virus via CD150 (SLAMF1) receptor infects immune cells located in the host respiratory tract such as macrophages and dendritic cells.{{Cite journal|last1=Ferreira|first1=Claudia S. Antunes|last2=Frenzke|first2=Marie|last3=Leonard|first3=Vincent H. J.|last4=Welstead|first4=G. Grant|last5=Richardson|first5=Christopher D.|last6=Cattaneo|first6=Roberto|date=2010-03-15|title=Measles Virus Infection of Alveolar Macrophages and Dendritic Cells Precedes Spread to Lymphatic Organs in Transgenic Mice Expressing Human Signaling Lymphocytic Activation Molecule (SLAM, CD150)|journal=Journal of Virology|language=en|volume=84|issue=6|pages=3033–3042|doi=10.1128/JVI.01559-09|issn=0022-538X|pmid=20042501|pmc=2826031}}{{Cite journal|last1=Leonard|first1=Vincent H.J.|last2=Sinn|first2=Patrick L.|last3=Hodge|first3=Gregory|last4=Miest|first4=Tanner|last5=Devaux|first5=Patricia|last6=Oezguen|first6=Numan|last7=Braun|first7=Werner|last8=McCray|first8=Paul B.|last9=McChesney|first9=Michael B.|last10=Cattaneo|first10=Roberto|date=2008-07-01|title=Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed|journal=The Journal of Clinical Investigation|volume=118|issue=7|pages=2448–2458|doi=10.1172/JCI35454|issn=0021-9738|pmc=2430500|pmid=18568079}}{{Cite journal|last1=Allen|first1=Ingrid V.|last2=McQuaid|first2=Stephen|last3=Penalva|first3=Rosana|last4=Ludlow|first4=Martin|last5=Duprex|first5=W. Paul|author-link5=William Paul Duprex|last6=Rima|first6=Bertus K.|date=2018-05-09|title=Macrophages and Dendritic Cells Are the Predominant Cells Infected in Measles in Humans|journal=mSphere|volume=3|issue=3|doi=10.1128/mSphere.00570-17|issn=2379-5042|pmc=5956143|pmid=29743202}} They transmit the virus to the lymphoid organs, from which it spreads systemically. In the later stages of infection, the virus infects other immune cell types, including B cells{{Cite journal|last1=Laksono|first1=Brigitta M.|last2=Grosserichter-Wagener|first2=Christina|last3=Vries|first3=Rory D. de|last4=Langeveld|first4=Simone A. G.|last5=Brem|first5=Maarten D.|last6=Dongen|first6=Jacques J. M. van|last7=Katsikis|first7=Peter D.|last8=Koopmans|first8=Marion P. G.|last9=Zelm|first9=Menno C. van|last10=Swart|first10=Rik L. de|date=2018-04-15|title=In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells|journal=Journal of Virology|language=en|volume=92|issue=8|pages=e00131-18|doi=10.1128/JVI.00131-18|issn=0022-538X|pmid=29437964|pmc=5874404}} and T lymphocytes{{Cite journal|last1=Koethe|first1=Susanne|last2=Avota|first2=Elita|last3=Schneider-Schaulies|first3=Sibylle|date=2012-09-15|title=Measles Virus Transmission from Dendritic Cells to T Cells: Formation of Synapse-Like Interfaces Concentrating Viral and Cellular Components|journal=Journal of Virology|language=en|volume=86|issue=18|pages=9773–9781|doi=10.1128/JVI.00458-12|issn=0022-538X|pmid=22761368|pmc=3446594}} also via SLAMF1 receptor.  In addition, it infects epithelial cells located in the airways. These cells become infected via nectin-4 receptor and by cell to cell contacts with infected immune cells. The infection of epithelial cells allows the virus to be released via the airstream.{{Cite journal|last1=Ludlow|first1=Martin|last2=Lemon|first2=Ken|last3=de Vries|first3=Rory D.|last4=McQuaid|first4=Stephen|last5=Millar|first5=Emma L.|last6=van Amerongen|first6=Geert|last7=Yüksel|first7=Selma|last8=Verburgh|first8=R. Joyce|last9=Osterhaus|first9=Albert D. M. E.|last10=de Swart|first10=Rik L.|last11=Duprex|first11=W. Paul|author-link11=William Paul Duprex|date=April 2013|title=Measles Virus Infection of Epithelial Cells in the Macaque Upper Respiratory Tract Is Mediated by Subepithelial Immune Cells|journal=Journal of Virology|volume=87|issue=7|pages=4033–4042|doi=10.1128/JVI.03258-12|issn=0022-538X|pmc=3624209|pmid=23365435}}{{Cite journal|last1=Singh|first1=Brajesh K.|last2=Li|first2=Ni|last3=Mark|first3=Anna C.|last4=Mateo|first4=Mathieu|last5=Cattaneo|first5=Roberto|last6=Sinn|first6=Patrick L.|date=2016-08-01|title=Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells|journal=Journal of Virology|language=en|volume=90|issue=15|pages=6808–6817|doi=10.1128/JVI.00266-16|issn=0022-538X|pmid=27194761|pmc=4944272}}

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{{Commons category}}

{{Wikispecies}}

• {{cite web |title=Measles virus |publisher=International Committee on Taxonomy of Viruses |url=http://www.ictvonline.org/virusTaxonomy.asp?src=NCBI&ictv_id=19750163}}

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{{Viral systemic diseases}}

{{Use dmy dates|date=April 2017}}

Category:Measles

Category:Morbilliviruses