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.[2]
Replication cycle
Entry
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.[3] For wild type and vaccine strains, extracellular domains of
CD150 (SLAM or SLAMF1)[4][5] and/or of
nectin-4 (also called Poliovirus-Receptor-Like 4 (PVRL4))[6][7] 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.[8][9]
Genome replication and viral assembly
Once the virus has entered a host cell, its strand of
negative sensessRNA 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.[10]
Genome and virion structure
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),[11] 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.[citation needed]
The measles virus evolved from the now eradicated
rinderpest virus which infected cattle.[12]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.[12]
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.[13] There is some linguistic evidence for an earlier origin within the seventh century.[11][14] The current epidemic strain evolved at the beginning of the 20th century—most probably between 1908 and 1943.[15]
Genotypes
The measles virus genome is typically 15,894 nucleotides long and encodes eight proteins.[16] 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.[citation needed]
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.[17]
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.[18]
Infection
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.[19][20][21] 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[22] and
T lymphocytes[23] 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.[24][25]
^CDC (5 November 2020).
"Measles is Easily Transmitted". Centers for Disease Control and Prevention. Retrieved 28 December 2023.
^Lu G, Gao GF, Yan J (2013). "The receptors and entry of measles virus: a review". Sheng Wu Gong Cheng Xue Bao (in Chinese). 29 (1): 1–9.
PMID23631113.
^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. Adherens junction protein nectin-4 is the epithelial receptor for measles virus.
OCLC806252697.{{
cite book}}: CS1 maint: multiple names: authors list (
link)
^Noyce, Ryan S.; Richardson, Christopher D. (20 June 2012). "Nectin 4 is the epithelial cell receptor for measles virus". Trends in Microbiology. 20 (9): 429–439.
doi:
10.1016/j.tim.2012.05.006.
ISSN0966-842X.
PMID22721863.
^
abGriffin DE (2007). "Measles Virus". In Martin, Malcolm A.; Knipe, David M.; Fields, Bernard N.; Howley, Peter M.; Griffin, Diane; Lamb, Robert (eds.). Fields' virology (5th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
ISBN978-0-7817-6060-7.