Mumps Virus: Molecular Aspects and Its Effects on the Central Nervous System

Author(s):  
M. Neal Waxham
2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Marie Kubota ◽  
Rei Matsuoka ◽  
Tateki Suzuki ◽  
Koji Yonekura ◽  
Yusuke Yanagi ◽  
...  

ABSTRACT Mumps virus (MuV) is an important aerosol-transmitted human pathogen causing epidemic parotitis, meningitis, encephalitis, and deafness. MuV preferentially uses a trisaccharide containing α2,3-linked sialic acid as a receptor. However, given the MuV tropism toward glandular tissues and the central nervous system, an additional glycan motif(s) may also serve as a receptor. Here, we performed a large-scale glycan array screen with MuV hemagglutinin-neuraminidase (MuV-HN) attachment proteins by using 600 types of glycans from The Consortium for Functional Glycomics Protein-Glycan Interaction Core in an effort to find new glycan receptor motif(s). According to the results of the glycan array, we successfully determined the crystal structures of MuV-HN proteins bound to newly identified glycan motifs, sialyl LewisX (SLeX) and the oligosaccharide portion of the GM2 ganglioside (GM2-glycan). Interestingly, the complex structures showed that SLeX and GM2-glycan share the same configuration with the reported trisaccharide motif, 3′-sialyllactose (3′-SL), at the binding site of MuV-HN, while SLeX and GM2-glycan have several unique interactions compared with those of 3′-SL. Thus, MuV-HN protein can allow an additional spatial modification in GM2-glycan and SLeX at the second and third carbohydrates from the nonreducing terminus of the core trisaccharide structure, respectively. Importantly, MuV entry was efficiently inhibited in the presence of 3′-SL, SLeX, or GM2-glycan derivatives, which indicates that these motifs can serve as MuV receptors. The α2,3-sialylated oligosaccharides, such as SLeX and 3′-sialyllactosamine, are broadly expressed in various tissues, and GM2 exists mainly in neural tissues and the adrenal gland. The distribution of these glycan motifs in human tissues/organs may have bearing on MuV tropism. IMPORTANCE Mumps virus (MuV) infection is characterized by parotid gland swelling and can cause pancreatitis, orchitis, meningitis, and encephalitis. MuV-related hearing loss is also a serious complication because it is usually irreversible. MuV outbreaks have been reported in many countries, even in high-vaccine-coverage areas. MuV has tropism toward glandular tissues and the central nervous system. To understand the unique MuV tropism, revealing the mechanism of receptor recognition by MuV is very important. Here, using a large-scale glycan array and X-ray crystallography, we show that MuV recognizes sialyl LewisX and GM2 ganglioside as receptors, in addition to a previously reported MuV receptor, a trisaccharide containing an α2,3-linked sialic acid. The flexible recognition of these glycan receptors by MuV may explain the unique tropism and pathogenesis of MuV. Structures will also provide a template for the development of effective entry inhibitors targeting the receptor-binding site of MuV.


2015 ◽  
Vol 25 (2) ◽  
pp. 209-226 ◽  
Author(s):  
Heidi V.N. Küsters-Vandevelde ◽  
Benno Küsters ◽  
Adriana C.H. van Engen-van Grunsven ◽  
Patricia J.T.A. Groenen ◽  
Pieter Wesseling ◽  
...  

PEDIATRICS ◽  
1960 ◽  
Vol 25 (5) ◽  
pp. 788-797
Author(s):  
Edwin H. Lennette ◽  
Gerald E. Caplan ◽  
Robert L. Magoffin

Eleven cases clinically considered to be mild paralytic poliomyelitis are reported in which there was clearcut serologic evidence of mumps virus infection. Poliomyelitis viruses were not isolated from the stools and complement-fixing and neutralizing antibodies to poliomyelitis were either absent (4 cases) or did not significantly change in titer between the acute- and convalescent-phase specimens of serum. Clinically, fever, headache, vomiting, nuchal rigidity, stiff back, muscle pain and slight to moderate weakness of several muscle groups were prominent manifestations. The cerebrospinal fluid uniformly contained over 100 leukocytes and commonly over 300, predominantly lymphocytes. Only 2 of the 11 cases developed evidence of parotitis, and in these, parotitis did not antecede the central nervous system manifestations. Electroencephalograms were abnormal in 3 of 8 cases. All 11 cases had evident muscle weakness at the end of the acute phase of illness, and four had slight residual weakness on convalescent examination 2 to 5 months after onset. There was no significant predilection for any muscle group. These observations emphasize that central nervous system involvement with the virus of mumps may be manifested as a syndrome of meningomyelitis and be erroneously diagnosed as paralytic poliomyelitis. Weakness is usually highly transitory but residual involvement may persist for some months. As the incidence of paralytic poliomyelitis is reduced by widespread immunization mumps virus may assume increasing relative importance as a cause of "poliomyelitis-like" disease.


Author(s):  
Gladys Harrison

With the advent of the space age and the need to determine the requirements for a space cabin atmosphere, oxygen effects came into increased importance, even though these effects have been the subject of continuous research for many years. In fact, Priestly initiated oxygen research when in 1775 he published his results of isolating oxygen and described the effects of breathing it on himself and two mice, the only creatures to have had the “privilege” of breathing this “pure air”.Early studies had demonstrated the central nervous system effects at pressures above one atmosphere. Light microscopy revealed extensive damage to the lungs at one atmosphere. These changes which included perivascular and peribronchial edema, focal hemorrhage, rupture of the alveolar septa, and widespread edema, resulted in death of the animal in less than one week. The severity of the symptoms differed between species and was age dependent, with young animals being more resistant.


Author(s):  
John L.Beggs ◽  
John D. Waggener ◽  
Wanda Miller ◽  
Jane Watkins

Studies using mesenteric and ear chamber preparations have shown that interendothelial junctions provide the route for neutrophil emigration during inflammation. The term emigration refers to the passage of white blood cells across the endothelium from the vascular lumen. Although the precise pathway of transendo- thelial emigration in the central nervous system (CNS) has not been resolved, the presence of different physiological and morphological (tight junctions) properties of CNS endothelium may dictate alternate emigration pathways.To study neutrophil emigration in the CNS, we induced meningitis in guinea pigs by intracisternal injection of E. coli bacteria.In this model, leptomeningeal inflammation is well developed by 3 hr. After 3 1/2 hr, animals were sacrificed by arterial perfusion with 3% phosphate buffered glutaraldehyde. Tissues from brain and spinal cord were post-fixed in 1% osmium tetroxide, dehydrated in alcohols and propylene oxide, and embedded in Epon. Thin serial sections were cut with diamond knives and examined in a Philips 300 electron microscope.


Author(s):  
Ezzatollah Keyhani

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.


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