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Mumps is a sudden infectious disease transmitted by the mumps virus (MuV). An enveloped, segmentless, negative-sense RNA virus, MuV moves in respiratory droplets and is extremely neurotropic. MuV is a member of the Paramyxoviridae, which includes the measles virus and canine distemper virus. The viral particles are cylinder-shaped — between 150 and 250 nanometres across — and each particle's surface is coated with a lipid bilayer. It contains 15,384 nucleotides in its genome, mostly negative-sense RNA. MuV consists of seven transcription factors: the nucleoprotein (N), the V/P/I complex, the matrix protein (M), the fusion protein (F), the small hydrophobic protein (SH), the hemagglutinin-neuraminidase (HN), and the large (L) protein. MuV is copied via the ribonucleoprotein (RNP) complex, and it enters host cells by binding HN and F proteins to sialic acid on the surface of host cells, thus enabling viral entry, replication and budding. The SH protein is also involved in immune escape, suppressing inflammation. In MuV infection, the virus initially enters through the respiratory system, where the viruses attach to sialic acid on the cell surface, and cause the cell membrane to fuse. MuV is then transcribed and replicated inside the cell via the RNP complex, and the virus circulates via budding. The mechanism for MuV is undetermined, but studies have shown that the virus invades respiratory epithelial cells and spreads through the upper respiratory tract. In the beginning, MuV is transmitted to the local lymph nodes, and then to the blood, creating viremia. The virus can infect many tissues throughout the body, its major target sites being parotid glands, testes, ovaries, CNS, kidneys and pancreas. The virus's hyper-neurotropism permits its entry into the CNS. Research has revealed that, of those infected, roughly half will develop central nervous system involvement, the vast majority of cases asymptomatic or mild. But the worst cases lead to aseptic meningitis or encephalitis. In addition, MuV can cause organ damage by immune processes including orchitis, mastitis, and nephritis. Even though we don't know MuV's complete pathogenesis, animal studies and clinical reports have revealed some details about the transmission pathways and associated pathology of MuV.
Clinical symptoms of MuV vary, but the most defining symptom is parotid swelling. Half to 80% of the patients present with bilateral parotid swelling, which is commonly accompanied by fever, headache, and weakness. Parotid swelling usually starts 2 to 3 weeks after infection, and typically lasts 2–3 days (with more severe cases lasting longer). The swelling is accompanied by swelling and bleeding of the salivary glands and symptoms of dry mouth and hunger. Along with parotid edema, MuV can infect other tissues and organs. Orchitis is the most widespread extra glandular form of mumps, usually found in post-pubertal males, and orchitis occurs in between 10% and 20% of patients. Orchitis can cause infertility problems – oligospermia and infertility. Women can suffer from oophoritis and mastitis, though they are uncommon. MuV-induced encephalitis or meningitis may affect the CNS. Despite the fact that very few of these cases display clear neurological signs, meningitis remains one of the most fatal complications of MuV infection and a leading cause of encephalitis in unvaccinated patients. MuV infection can cause deafness as well; about 4% of patients become deaf, especially in children. This hearing loss is unilateral and generally short-lived (although sometimes permanent).
Figure 1. Clinical Manifestations and Pathogenesis of Mumps Virus (Source: Rubin, S., et al., 2015)
The incidence of mumps has fallen drastically since the mumps vaccine was first introduced in the late 1960s in the US. The incidence in the United States had nearly ceased, down more than 99.9%, by 2001. Other countries have had similar contagion benefits from vaccination. But mumps has occasionally been seen in populations recently vaccinated — especially those with high rates of vaccine coverage. It is also questionable whether the vaccine can be effective because some strains of the virus can actually evade immune systems, and thus the vaccine cannot work. Studies indicate that the long-term immune efficacy of the mumps vaccine is falling apart, and cases of meningitis caused by vaccine strains have raised safety issues. With a growing focus on vaccine effectiveness, certain vaccine strains have been pulled, and in some cases the mumps vaccine was no longer included in national vaccination programs. In Japan, for instance, the mumps vaccine was dropped from the national immunisation schedule, and Japan became one of the countries with the highest mumps rates. Although widespread availability of the mumps vaccine reduced the prevalence of mumps, vaccinated losses and the appearance of viral variants revived interest in the pathogenesis of MuV, immune defences and vaccines. Researchers should explore the full extent of MuV's spread in the body, particularly in the central nervous system, in the future. Additionally, there will be focus on advancing novel vaccines and therapeutics for viral variants and immune evasion. In order to do a better job in dealing with mumps outbreaks and vaccine problems, researchers also need to learn more about MuV's pathogenesis through animal models, its pathways into the body, its immunity against it, and how it works with other immune systems. Such studies will enable us to create better, safer vaccines and reduce the burden of mumps on public health. So, all in all, MuV is the main cause of mumps and because of its strong neurotropism and multi-organ involvement, it has the potential to induce a diverse array of extreme clinical manifestations. Although mumps has become dramatically less prevalent through widespread vaccination, declining vaccine efficacy and viral mutations have led to fresh questions about MuV's cause. We will continue to study the virus' immune escape, how best to make vaccines, and how we can create novel therapeutic strategies to control the virus and minimise the impact on public health.
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