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22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2NTRODUCTIONAcute measles is normally a mild disease contracted by children and young adults as a result of infection by the highly contagious measles virus (MV) (ter Meulen and Billeter. 1995). MV IS an efficient pathogen, persisting in nature in populations large enough to support it, even though i (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2t causes an acute infection in any individual only once in a lifetime. Despite this, the virus is distributed worldwide and IS antigenically stable. W(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
ith the advent of molecular epidemiology, however, the existence of MV genotypes has been confirmed. MV has no animal reservoir. and although monkeys 22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2r years in a single individual, yet these infections are rare and not associated with periodic shedding of infectious vims as seen with herpesviruses. A single attack of measles IS sufficient to confer lifelong immunity to clinical disease upon reinfection, even in the absence of re-exposure to the (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2virus. Consequently, in order to remain endemic in a given community, the virus must rely on the infection of the young who are still susceptible. So(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
efficient is the process that the first known report of measles (in Egyptian hieroglyphics) failed to recognize the infectious nature of the illness, 22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2een in children aged five to nine years. Infections and epidemics centred around elementary schools, and younger children acquired measles as secondary cases from their school-age siblings. By the age of 20. approximately 99% of subjects tested had been exposed to MV. With the introduction of the me (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2asles vaccine the age incidence and percentage of cases indifferent age groups has changed markedly. In countries with an optimal vaccine utilization,(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
measles infection has shifted to the teenage group, whereas in areas with ineffective vaccine progranunes cliildren up to four years of age reveal a 22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2est incidence in children under two years of age. Here, case fatality rates range from 1 to 5% and can reach 30% in refugee camps and comparable settings, with malnour-ishment. crowding and intensity of exposure being major determinants of Severity and mortality (Moss. 2007). Although a safe and eff (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2icient vaccine has been available for over four decades, measles still is a leading cause of death for young children. The Measles Initiative, a partn(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
ership between the World Health Organization (WHO), the United Nations, the US Centers for Disease Control and Prevention (CDC). the American Red Cros22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2ity reduction. As a result, measles deaths worldwide fell from an estimated 873 000 (1999) to 345 000 in 2005 (Wolfson etal., 2007; www.measlesinitiative.orginde.x3.asp).THE VIRUSAlthough measles lias been known for centuries, it was only with the isolation of the virus by Enders and Peebles in 1954 (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2 that experimentation became possible. The development of tissue culture systems, the availability of monoclonal antibodies and molecular biological a(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
pproaches then permitted insight into viral structure and replication. Functional studies on MV' control regions andPnncípỉeĩ and Practice of CíMtcaí 22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 20^1799-4534Principles and Practice of Clinical Virology, Sixth EditionGene boundaryDistal geneBicistromc and genomic RNAsmRNAsProximal gene »(0Figure 22.1 (a) Diagrammatic representation of the measles virus panicle, (b) MV mRNAs are sequentially transcribed from the genome with decreasing efficienc (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2y and encode the structural proteins. In addition, the second gene (the p gene) encodes three nonstroctural viral proteins c. R and V. (c) At the gene(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
boundaries. MV genes are separated by conserved intergenic regions where the polymerase complex stutters to polyadenylate the proximal mRNA to subseq22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2re transcribed as well as during genome replication.Measles Virus535proteins extensively benefited from the establishment of a plasmid-driven reverse genetic system which allowed construction and rescue of infectious MVs in tissue culture that cany stable alterations in their genomes ( Radecke er al (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2., 1995). Thus, within limitations imposed by the fitness of the mutated recombinant virus, the contribution of single viral gene products within the(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
viral life cycle in tissue culture, but also in experimental infection in animals can be addressed. Meanwhile, a plethora of recombinant MV's have bee22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2experimental infection, and cytokine genes. Moreover, targeted interaction of recombinant MV with its naniral or other, desired host cell receptors has been widely studied to gain insight into basic determinants of viral tropism, but also for potential application of systemic, targeted delivery’ in (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2cytoreductive regimens for malignancies (lankov er al., 2007). The use of recombinant MV carrying heterologous viral genes (e.g. simian immunodeficien(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
cy vims (SIV) or human immunodeficiency vims I HIV) genes) as multivalent vectors for immunization has been explored, although this lias been limited 22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2ldae, Henipavirldae. Bornaviridae and Parannxavindae. As a paramyxovirus. MV has structural and biochemical features associated with this group, but because It lacks a virion-associated neuraminidase activity it is grouped into a separate genus. Morbillivirus. of which Measles virus is the type spec (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2ies. Other members include: Peste-des-petits-nnninants virus (PPRV). which infects sheep and goats. Rinderpest virus (RPV), which infects cattle, Canu(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
te distemper virus (CDV). which infects dogs. Phocine distemper virus (PDV), which infects seals and sea-lions. Dolphin morbiỉlivinis (DMV) and Porpoi22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2persist in the central nervous system (CNS) in their natural hosts and produce chronic neurological diseases.VIRUS MORPHOLOGYMeasles virus particles consist of a lipid envelope surrounding the viral ribonucleoprotein (RNP) complex, which is composed of genomic RNA associated with proteins (Figure 22 (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2.1a). The MV transmembrane fusion (F) and haemagglutinin (H) proteins project from the envelope surface of the panicle, extend through the lipid bilay(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
er into the cytosol. It is the N-terminus of the Hprotein that protrudes through the cytoplasmic and viral membranes (type II glycoprotein), while the22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2ionally with the matrix (M) protein (Taliara et al.. 2007), which, in turn, links the envelope to the RNP core structure. The viral genomic RNA is fully condensed with N (nucleocapsid) protein to form the RNase-resistant RNP core structure. In vitro experimentation suggests that the virion is able t (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2o package more than one genome as long as the ’rule of six’ (see below) is maintained (Rager er al.. 2002). As the viral genome cannot serve as mRNA.(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
the viral polymerase complex consisting of the p (phospho-) and L (large) proteins is part of the RNP core. Their location within this complex is as y22Measles VirusSibylle Schneider-Schaulies and Volker ter MeulenDepartment of virology and Immunobiology. University of Wurzburg, Wiirzburg, GermanyIN (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2ze of 120-250 Iim. In an electron micrograph tlie virion is bounded by a lipid envelope which bears a fringe of spike-like projections (peplomers) 5-8 nm long (Figure 22.2a). The membrane below the spikes is 10-20mn thick and encloses the helical viral RNP core which has a diameter of 17 nm and a re (mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2gular pitch of 5 nm. Immediately below the membrane M proteins appear as a shell of electron-dense material.GENOME STRUCTUREThe viral genome IS a nons(mebooksfree.com)priamp;praamp;cliamp;viramp;zucamp;banamp;griamp;schamp;moramp;6th 2
egmented RNA molecule of negative polarity that is about 16 kb in length. The genome encodes SIX structural genes for which the reading frames are arrGọi ngay
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