Picornaviruses - Educational Materials

Picornaviruses Properties of Picornairuses  They are a vary large virus family with respect to the number of members (>230 members)  They are one of the smallest in terms of virion size(28-30 nm in diameter)  Their genome is not complex  Virion has icosahedral symmetry, contains 60 subunits  Genome is single-stranded RNA, linear and positive sense.  Genome contains genome linked protein(VPg)  Envelope: None  Replication : Cytoplasm • The virion consists of a capsid shell of 60 subunits, each of four proteins (VP1-VP4) around a single-stranded RNA • But Parechoviruses contain only three proteins because VP0 does not get cleaved into VP2 and VP4 This diagram shows internal location of the RNA genome surrounded by capsid composed of pentamers of proteins VP1, VP2, VP3 and VP4. Note the canyon depression surrounding the vertex of the pentamer Canyon= receptor binding site Used to attach the virion to a host cell The canyon is too narrow to permit deep penetration of antibody molecules The organization of the genome is similar for all The genome is polyadenylated at the 3 end has a small viral- coded protein (VPg) cvalently bound to the 5 rnd The pisitive-sense genomic RNA is infectious Classification • • • • • • The Picornaviridae family contains 12 genera, The most important are: Enterovirus: polioviruses(types 1-3), coxsackieviruses of group A and B, echoviruses, enteroviruses(types 68-116, no type 72), rhinoviruses Hepatovirus: hepatitis A virus Kobuvirus: Aichi virus Parechovirus: parechoviruses Aphtovirus: foot-and-mouth disease viruses Picornavirus Replication • The picornavirus replication cycle occurs in the cytoplasm of cells • 1- attachment to a specific receptor in the plasma membrane ( poliovirus and human rhinovirus: members of the immunoglobulin gene superfamily, and echoviruse: integrin adhesion superfamily) • 2- Receptor binding triggers a conformational change in the virion which results in release of the viral RNA into the cell cytosol Translation VPg is removed from the viral RNA as it associates with ribosomes The infecting viral RNA is translated into a polyprotein This polyprotein is rapidly cleaved into fragments by proteinases encoded in the polyprotein -The infecting viral RNA strand is copied -Complementary strand serves as template for the synthesis of new plus strands -Many plus strands are generated from each minus-strand template Maturation -Maturation involves several cleavage events -Coat precursor protein P1 is cleaved to form aggregates of VP0, VP3, and VP1 - These protomers assemble into pentamers that package plus-strand VPg-RNA to form provirions - The provirions are not infectious until a final cleavage changes VP0 to VP2 and VP4 - The mature virus particles are released when the host cell disintegrates -The multiplication cycle for most picornaviruses takes 5-10 hours Enterovirus Group • Polioviruses: • Poliomyelitis is an acute infectious disease that in its serious form affects the central nervous system(CNS) • The destruction of motor neurons in the spinal cord results in flaccid paralysis • Most poliovirus infections are subclinical • Polioviruses have a vary restricted host range • • Poliovirus requires a primate-specific membrane receptor for infection Antigenic • There are three antigenic types of polioviruses based on epitopes found in the VP1,VP2, and VP3 proteins Pathogenesis and Pathology • The mouth is the portal of entry of the virus • Primary multiplication takes place in the oropharynx or intestine • The virus is regularly present in the throat and in the stools before the onset of illness • One week after infection, there is little virus in the throat, but virus continues to be excreted in the stools for several weeks • The virus first multiplies in the tonsils, the lymph nodes of the neck, Peyer,s patches, and the small intestine • Poliovirus can spread along axons of peripheral nerves to the CNS • Poliovirus does not multiply in muscle in vivo. • The changes that occur in peripheral nerves and voluntary muscles are secondary to the destruction of nerve cells Clinical Findings • • Most infections are subclinical, only about 1% of infections result in clinical illness The incubation period is usually 7-14 days, but it may range from 3 to 35 days • A. Mild Disease: the most common form of disease. The patient has only a minor illness B. Nonparalytic Poliomyelitis (Aseptic Meningitis): stiffness and pain in the back and neck, and recovery is rapid and complete C. Paralytic Poliomyelitis: Flaccid paralysis resulting from lower motor neurons damage. Maximal recovery occurs within 6 months, with residual paralysis lasting much longer D. Progressive Postpoliomyelitis Mussle Atrophy: decades after paralytic poliomyelitis, a result of phusiologic and aging ahanges in paralytic patints • • • Laboratory Diagnosis • The virus may be recovered from throat swabs taken soon after onset of illness and from rectal swabs or stool samples collected over long period • Poliovirus is uncommonly recovered from the cerebrospinal fluid • Virus isolation in the cell culture(human or monkey cell lines)→isolated virus is identified and typed by neutralization with specific antisera • Virus can also be identified more rapidly by PCR Prevention and Control Live attenuated vaccine(Sabin): -Mucosal immunity -Interference -The vaccine viruses(particularly types 2,3)may be mutate -Should not be administered to immunodeficient or immunosupressed individuals or their household contacts Formalin- inactivated vaccine(Salk): -Induces humoral antibodies but does not induce local intestinal immunity