Meningitis(common)/Encephalitis Non-polio enterovirusesParalyticpolio-like syndromeCoxsackie A7Herpangina: ulcerations onthe palate CoxsackieAHand-foot-mouth diseaseCoxsackieAMyocarditisand pericarditisCoxsackieBPleurodynia:inflammation of the intercotalmuscles CoxsackieBCoxsackie A virus does not grow in vitro. •Two vaccines available: (1) liveattenuated vaccine, (2) killed vaccine •Antibody in the blood protects against disease •Mucosal antibody protects against infection Binding and Entry CD155 on the host cell membrane binds the cleft between VP1 and VP2. As the virus is endocytosed, it undergoes conformational change leading to the release of VP4. RNA passes across the membrane into the cytoplasm. RNA Replication and Protein Synthesis Replication takes place in the cytoplasm and can occur in cells that do not have a nucleus. The RNA, which has a 5’ IRES, serves as a translation template. One of the proteins produced is an RNA-dependent RNA polymerase that generates a complementary minus sense RNA which serves as a template for more plus strand RNA synthesis. Minus strand synthesis is primed by Vpgprotein that has been modified by uridines. Virus MaturationViral protease cuts polyproteinprecursor into mature proteins. Capsidproteins assemble in the cytoplasm, packaging plus strand RNA with VPgprotein on it. Viral replication complex assembly occurs on cytoplasmicmembranes, which provide localization and increase efficiency. CytopathicEffect Polioviruses cause cell rounding, shrinkage, and nuclear changes consistent with apoptosis in the cells that they infect. The virus shuts off host protein synthesis by proteolyticallycleaving the host translation initiation factor eIF4g. Antibodies to Poliovirusneutralize the virus by binding to several different surface neutralization sites. Chemically Inactivated VaccineLiveAttenuated Vaccine AdministrationIntramuscularinjectionOralProtectionDisease only (IgG)Disease (IgG)Infection (IgA)TransmissionNoYesSafefor Immunodeficient?YesNoCancause disease if properly handledNoYesHerd Immunity?NoYes Attenuated Vaccine Production: Live attenuated vaccine is formed by serial passage of serotypes 1 and 3 through monkey kidney cells at subphysiologictemperature, followed by screening for reduced virulence (serotype 2 is naturally low virulence). Mutations that result in attenuation are in (1) the capsidproteins, or (2) the 5’ IRES sequence. When live attenuated vaccine reverts to the virulent form, this often occurs at site 472, the site of binding for polypyrimidinetract binding protein (PTB), which is required for initiation of translation. PTB is present in lower levels in the neurons than in the intestinal cells. HemorrhagicconjunctivitisEnterovirus70CoxsackieA 24 Properties of picornaviruses•Icosahedralsymmetry with 60 capsomereseach composed of 4 polypeptides (VP1-4) .