Mumps virus

Structure of Mumps Virus

•    Mumps virions are markedly pleomorphic (100 to 600 nm), and roughly spherical with an outer membrane that envelops an inner, coiled helical structure.
•     The envelope which is 150 to 300nm is studded with projections formed by the viral glycoproteins that rise 12 to 15 nm from the virion surface.
•     The coiled inner structure or nucleocapsid is a ribonucleoprotein complex that appears to be a hollow tube with a unit length of approximately 1 μm, a diameter of 17 nm, and a central core of 5 nm.
•     The nucleocapsid consists of the negative-sense, single-stranded RNA associated with the nucleoprotein (NP), polymerase phosphoprotein (P), and large (L)
•     The L protein is the RNA polymerase, the P protein facilitates RNA synthesis, and the NP protein helps maintain genomic structure.
•     The nucleocapsid associates with the matrix (M) protein lining the inside of the virion envelope.
•     The envelope contains two glycoproteins, a fusion (F) protein, which promotes fusion of the viral and host cell membranes, and a viral attachment protein (hemagglutinin-neuraminidase [HN], hemagglutinin [H], or glycoprotein [G] protein).
•     Full-length genomic RNA is an unsegmented, single-stranded macromolecule of negative polarity.

Genome of Mumps Virus

• 
  
•  The genome is monopartite, unsegmented single stranded RNA with negative polarity that contains about 15.3 kilobases.
• The virus contains six major structural proteins: nucleocapsid-associated protein (NP), phosphoprotein (P), and polymerase protein (L) are associated with the nucleocapsid; membrane or matrix (M) protein; and two glycoproteins, a hemagglutinin-neuraminidase (HN) and a fusion (F) molecule.
• The virus genes have been sequenced and the gene order for mumps virus is 3’-NP–P–M–F–SH–HN–L-5’.
•  There is a nontranscribed leader sequence of 55 nucleotides and a trailing sequence of 24 nucleotides that share inverse complementarity at their extremes.

Replication of Mumps Virus 

•     Virions attach via the HN protein to cellular sialoglycoproteins or glycolipid receptors.
•     The F protein then mediates fusion of the viral envelope with the plasma membranes at physiological pH and ribonucleocapsid is released in the cytoplasm.
•     The liberated nucleocapsid remains intact, and all three associated proteins (N, P, and L) are required for the transcription of the incoming viral genome.
•     This nucleocapsid structure thus acts as a template for the initiation of infection through a process of transcription of viral mRNA from the negative-sense viral RNA.
•     During the early stages of the replication cycle, the viral genome directs the synthesis of a (+) sense leader and six to ten discrete, unprocessed mRNA species.
•     The mRNAs are capped and polyadenylated.
•     When the concentration of N protein reaches a critical level it binds to the nascent (+) sense antigenome intermediates, with the result that the polyadenylation, termination, and reinitiation of full-length RNA molecules is prevented and transcription then switches to the replication of full-length genome intermediates: these in turn serve as templates for the production of nascent full-length (–) sense viral genomes.
•     Newly synthesized RNA associates with the N proteins and L protein to form helical nucleocapsids.
•     The ribonucleocapsid interacts with the matrix protein under the plasma membrane and buds via the ESCRT complex, releasing the virion.

Pathogenesis of Mumps Virus

•    Natural infection is initiated by droplet spread.
•     Primary replication occurs in nasal or upper respiratory tract epithelial cells.
•     Viremia then disseminates the virus to the salivary glands and other major organ systems.
•     The incubation period may range from 2 to 4 weeks but is typically about 14–18 days.
•     Virus is shed in saliva for as long as 6 days before the onset of parotitis.
•     About one-third of infected individuals does not exhibit obvious symptoms but are equally capable of transmitting infection.
•     Termination of viral excretion in saliva correlates with the local appearance of virus-specific secretory IgA, as early as 5 days after disease onset.
•     Virus-specific IgM antibodies are also present early in saliva.
•     Thus, patients with mumps are capable of spreading virus by the respiratory route over a 7 to 10 days interval.
•     A cell-mediated immune response also develops.
•     Interferon is induced early in mumps infection.
•     Plasma viremia disappears coincident with the development of mumps virus–specific humoral antibody, which can be detected in serum as early as 11 days after induced apparent or inapparent infection of humans.
•     Mumps virus preferentially infects activated human T lymphocytes.
•     Mumps is a systemic viral disease with a propensity to replicate in epithelial cells in various visceral organs.
•     Virus frequently infects the kidneys and can be detected in the urine of most patients.
•     Viruria may persist for up to 14 days after the onset of clinical symptoms.
•     The central nervous system is also commonly infected and may be involved in the absence of parotitis.
•     Viral invasion of the CNS presumably occurs across the choroid plexus.
•     Blood-borne infected mononuclear cells may cross the fenestrated endothelium of the choroid plexus stroma and serve as a source for subsequent infection of the choroidal epithelium.
•     Maturation of virus from the ventricular surfaces of choroidal cells provides progeny virions that are widely distributed through ventricular pathways and the subarachnoid space by CSF.

LAB DIAGNOSIS

• Lab studies not required to establish diagnosis of typical cases, however may sometimes be confused with enlargement of parotids due to suppuration, drug sensitivity, tumors etc.
• Isolation and identification of virus
• –  saliva, CSF, urine collected with in few days after onset of illness
• –  monkey kidney cells preferred for viral isolation; samples should be inoculated shortly after collection.
• –   For rapid diagnosis, IFT to detect viral Ag in 2-3 day cell culture.
• –   Virus produces little CPE (cell rounding, giant cell formation)
• –  Haemadsorption test to demonstrate presence of haemadsorbing agent.

Serology

• Ab- rise detected using paired sera; ELISA or HI test commonly used.
• –   Mumps IgM present, early in illness and lasts for 60 days; the heterotypic Ab induced by parainfluenza virus infection don’t cross- react in mumps IgM, ELISA.
• –  CFT using S- and V- Ag is also performed.

Epidemiology

• –   endemic worldwide; disease incidence highest in children aged 5-9 yrs.
• –  Humans are the only natural hosts; transmission by direct contact, air- borne droplets or contaminated fomites.
• –  Subclinical cases can transmit the virus.
• –  Mortality rate is low (0.01%), mostly due to encephalitis.

Treatment / Prevention / control:

• –  no specific therapy
• –  immunization with attenuated live mumps vaccine ( made in chick embryo culture) produces a subclinical , non communicable infection; it is available in monovalent form ( mumps only) or in combination with measles and rubella (MMR vaccine) and given as single subcutaneous injection ; provides protection for at least 10 yrs.
• –   Vaccine contains the Jeryl Lynn or Urabe strains.
• –    Contraindications are pregnancy, immunodeficiency and hypersensitivity to neomycin and egg protein.
• Passive immunization not very reliable.