Protection of non-murine mammals against encephalomyocarditis virus using a genetically engineered Mengo virus

Osorio, Jorge E.; Hubbard, Gene B.; Soike, Kenneth F.; Girard, Marc; Werf, Sylvie van der; Moulin, Jean Claude; Palmenberg, Ann C.

doi:10.1016/0264-410x(95)00129-o

Cited by 32 publications

(35 citation statements)

References 11 publications

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“…All intermediate-tract mengoviruses show correspondingly diminished virulence. For viruses with poly(C) tracts between 25 and 35 bases, the LD 50 in mice increases about 1 log 10 PFU for every 3 C's that are removed from the tract (13,20). For EMCV strains, the correlation between tract length and murine virulence is weaker, however, and the poly(C) needs to be truncated substantially (i.e., ϽC 9 ) before the attenuation becomes measurable (e.g., the LD 50 of vEC 4 is 3 ϫ 10 3 PFU compared to 1 PFU for EMCV-R) (9).…”

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Mengovirus and Encephalomyocarditis Virus Poly(C) Tract Lengths Can Affect Virus Growth in Murine Cell Culture

Martin

Neal

McBride

et al. 2000

J Virol

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Encephalomyocarditis virus (EMCV) and mengovirus are serotypically related cardioviruses of the picornavirus family. Among the unusual features of their positive-sense singlestranded RNA genomes are long 5Ј untranslated polypyrimidine tracts [poly(C)] with sequences consisting of C 115 UCUC 3 UC 10 and C 44 UC 10 for EMCV (strain R) and mengovirus (strain M), respectively (6, 13). These cardioviruses and their closely related cousins, the foot-and-mouth disease viruses of the Aphthovirus genus, are the only known eukaryotic or prokaryotic genomes to contain such poly(C) tracts, and the specific function of the homopolymer region remains a biological enigma.We have reported the construction of multiple cDNA-derived EMCV and mengovirus strains which differ from each other and from wild-type parental strains only in the lengths of their 5Ј poly(C) tracts (8, 9, 13). The mengovirus panel included nine viruses with poly(C) lengths that ranged from C 44 UC 10 (vMwt) down to a precise deletion of all the cytidine residues (vMC 0 ). The EMCV panel (vEC 20 , vEC 9 , and vEC 4 ) was less extensive, although it contained representative analogues for the best-characterized mengovirus strains. As a definitive phenotype, deletion of the mengovirus poly(C) tract clearly correlates with attenuation of virus virulence in animals. vMC 0 , for example, has a median 50% lethal dose (LD 50 ) of Ͼ2 ϫ 10 9 PFU after intracerebral inoculation of mice. In contrast, the LD 50 of vMwt by equivalent inoculation is only 10 PFU (7). All intermediate-tract mengoviruses show correspondingly diminished virulence. For viruses with poly(C) tracts between 25 and 35 bases, the LD 50 in mice increases about 1 log 10 PFU for every 3 C's that are removed from the tract (13,20). For EMCV strains, the correlation between tract length and murine virulence is weaker, however, and the poly(C) needs to be truncated substantially (i.e., ϽC 9 ) before the attenuation becomes measurable (e.g., the LD 50 of vEC 4 is 3 ϫ 10 3 PFU compared to 1 PFU for EMCV-R) (9). Our EMCV and mengovirus recombinant isolates have been extensively characterized for growth in HeLa cells, and all were found to plaque with equivalent plating efficiencies regardless of the poly(C) tract length. While some strains do exhibit subtle changes in plaque size that correlate with incremental tract deletion (9, 13), none of the isolates show tract-dependent variations in replication kinetics or end-point titers when measured directly in single-step growth experiments. The poly(C) tracts also have no apparent influence on genome translation, virion stability, or growth temperature sensitivity, and it is clear, at least for growth in HeLa cells, that the major vegetative life cycle requirements for EMCV and mengovirus are not strongly vested in this region of the viral RNA.However, in infected animals, especially those receiving mengoviruses, there must be some cellular or tissue determinant that rapidly detects subtle differences in poly(C) genotype and reacts in a manner that clearly means l...

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Mengovirus and Encephalomyocarditis Virus Poly(C) Tract Lengths Can Affect Virus Growth in Murine Cell Culture

Martin

Neal

McBride

et al. 2000

J Virol

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“…Laboratory mice receiving the short-tract strains developed life-long protective immunity against normally lethal challenge with wildtype Mengo or EMCV (Osorio et al, 1996b). Vaccination with a variety short poly(C) Mengo viruses has been shown to protect macaques, baboons and domestic swine as well as mice when challenged with wildtype EMCV (Osorio et al, 1996a). The objective of the current project was to determine whether inoculated target species at the Audubon Park Zoo and Miami Metro Zoological Park.…”

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“…For intramuscular inoculation studies, suspensions of HeLa cells infected with vMC0 were clarified by centrifugation (10,000 g for 30 min, 4C), followed by ultra centrifugation through a 30% sucrose cushion. The resuspended pellet was stored at 4 C (Osorio et al, 1996a (Hystrix africaeaustralis). The animals were injected intramuscularly during annual physical examinations with 5.0 ϫ 10 6 PFU (plaqueforming units) of the prepared supernatant.…”

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“…Serum samples were stored at Ϫ20 C until analysis. Samples were tested by two independent laboratories for serum microneutralization titers to EMCV using 2 fold serial dilutions of serum samples (Hubbard et al, 1992;Osorio et al, 1996a). Seroconversion was considered to be a four fold increase in serum titer.…”

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“…One of the most important components of EMCV mortality prevention is an effective and consistent rodent control (Osorio et al, 1996a). A virulent challenge was deemed inappropriate in a zoological setting and was not performed.…”

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