Picornaviridae Lecture 8

Question 1

Picornaviridae

Answer 1

Genera: enterovirus, rhinovirrus

single stranded, non segmented RNA

+ polarity genome (can act as a messenger RNA). Genome = AUGGC; mRNA = AUGGC. Genome can transfect cells; naked genomic RNA is introduced into a cell and infection is initiated

RNA has poly A at 3’ end and VPg at 5’ end (VPg is not a cap structure)

Capsid has 4 structural proteins; VP1, VP2, VP3, VP4. Icosahederal capsid- NO ENVELOPE

capsid structure is stable to acid (enteroviruses) and the environment, rhinoviruses not acid stable (not enterovirus)

Question 2

Picornaviridae infection and replication

Answer 2

Attachment to cell receptor (PVR or CD155 immunoglobulin superfamily); lose VP-4 protein from capsid, penetration by endocytosis (viropexis)

uncoating: occurs in cytoplasm, which is the site of viral replication; VP1, VP2, and VP3 are removed from the virus particle to release the RNA genome

The viral genome is + polarity RNA and can serve as a messenger RNA; following loss of VPg the genomic RNA can be translated into viral proteins; genomic RNA associates with cellular ribosomal subunits for translation to occur cellular ribosomal subunits for translation to occur. The 5’ end of the viral mRNA consists of a specialized structure that facilitates translation. The structure designated “internal ribosome entry site” (IRES) consists of about 700 ribonucleotides and is essential for viral mRNA translation

Question 3

Picornaviridae infection and replication 2

Answer 3

Translation: formation of viral polyproteins (polyprotein is a tandem array of viral proteins linked together as one continuous large protein); poliovirus infection causes disruption of pre-existing cell polyribosomes to make ribosomes available for viral translation +RNA w/o VPg is translted into polyprotein P123, which is a precursor protein.

P123 is a proteolytically cleaved into both structural polypeptides and enzymes via a sequence of proteolytic cleavage steps.

Some of the celavage products will eventually end up as new capsid proteins. VPg is also a cleavage product. VIral protein 3d is the RNA dependent RNA polymerase, which combines with hostfactor (Hf)

Question 4

Picornaviridae infection and replication 3

Answer 4

Replication of genomic RNA: occurs in the cytoplasm

+RNA w VPg= RNA or replication. +RNA w/o VPg= mRNA that is translated

Replication: viral RNA polymerase + Host factor (Hf). RNA polymerase adn genomic RNA with VPg at its 5’ end is then involved in viral RNA replication. A replicative intermediate (RI) is formed due to the + genomic RNA being converted to many = RNAs; then full length, RNA is copied into + genomic RNAs (another RI).

VPO proteolytically cleaved to VP2 nd VP4 during viral maturation

assembly of infectious virus particles + production of empty capsids protein produced in excess; note empty capsids are not infectious; cell lysis occurs as an end result of infection

at the end of replication cycle each cell can yield approximately 10,000 virus particles.