Mumps pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]; Nate Michalak, B.A.

Overview

Humans are the only natural host for mumps virus (MuV). MuV is transmitted through respiratory droplets (saliva or mucus), direct contact, or contact with surfaces carrying MuV. MuV infects the upper respiratory tract epithelium by binding to extracellular sialic acid via the hemagglutinin-neuraminidase (HN) glycoprotein. MuV is able to evade an immune response with small hydrophobic (SH) protein, which blocks TNFα-mediated apoptosis, and with the V proteins, which inhibit IFN production and signaling. MuV disseminates through the lymphatic system to cause systemic infection. Replication in the parotid gland (or other salivary gland) causes mononuclear cell infiltration, hemorrhage, edema, and necrosis.

Pathophysiology

Transmission

Humans are the only natural host for mumps virus (MuV).
MuV is transmitted through respiratory droplets (saliva or mucus), direct contact, or contact with surfaces carrying MuV.
Mumps is contagious several days prior and up to 5 days after onset of parotitis.

Pathogenesis

MuV enters the body through inhalation or oral contact and infects the upper respiratory tract epithelium.^[1]
MuV is able to attach to extracellular sialic acid via the hemagglutinin-neuraminidase (HN) glycoprotein.
HN and the fusion (F) glycoprotein mediate cell membrane fusion, allowing viral material to enter respiratory epithelial cells.
HN and F, in conjunction with matrix (M) protein, are also involved in localizing viral material after replication and inducing virion budding.
MuV is able to inhibit an immune response to infection with the following virulence factors:

Small hydrophobic (SH) protein is presumed to block TNFα-mediated apoptosis.^[2]
Non-structural proteins NS1 and NS2 (V proteins) inhibit IFN production and signaling.^[3]

MuV disseminates through the lymphatic system to cause systemic infection.
Replication in the parotid gland (or other salivary gland) causes mononuclear cell infiltration, hemorrhage, edema, and necrosis.

Virulence Factors

Small hydrophobic (SH) protein: blocks TNFα-mediated apoptosis
Non-structural proteins NS1 and NS2 (V proteins): inhibit IFN production and signaling
Haemagglutinin-neuraminidase (HN) glycoprotein: binds with extracellular host cell sialic acid

Resources

CDC: Mumps Transmission

References

↑ Rubin S, Eckhaus M, Rennick LJ, Bamford CG, Duprex WP (2015). “Molecular biology, pathogenesis and pathology of mumps virus”. J Pathol. 235 (2): 242–52. doi:10.1002/path.4445. PMC 4268314. PMID 25229387.
↑ He B, Lin GY, Durbin JE, Durbin RK, Lamb RA (2001). “The SH integral membrane protein of the paramyxovirus simian virus 5 is required to block apoptosis in MDBK cells”. J Virol. 75 (9): 4068–79. doi:10.1128/JVI.75.9.4068-4079.2001. PMC 114152. PMID 11287556.
↑ Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S; et al. (2004). “The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter”. Proc Natl Acad Sci U S A. 101 (49): 17264–9. doi:10.1073/pnas.0407639101. PMC 535396. PMID 15563593.

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[pmid25229387-1] Rubin S, Eckhaus M, Rennick LJ, Bamford CG, Duprex WP (2015). “Molecular biology, pathogenesis and pathology of mumps virus”. J Pathol. 235 (2): 242–52. doi:10.1002/path.4445. PMC 4268314. PMID 25229387.

[pmid11287556-2] He B, Lin GY, Durbin JE, Durbin RK, Lamb RA (2001). “The SH integral membrane protein of the paramyxovirus simian virus 5 is required to block apoptosis in MDBK cells”. J Virol. 75 (9): 4068–79. doi:10.1128/JVI.75.9.4068-4079.2001. PMC 114152. PMID 11287556.

[pmid15563593-3] Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S; et al. (2004). “The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter”. Proc Natl Acad Sci U S A. 101 (49): 17264–9. doi:10.1073/pnas.0407639101. PMC 535396. PMID 15563593.

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