RNA Viruses and RNA Templates

A set of vocabulary-style flashcards covering key terms, definitions, and concepts from the lecture on RNA viruses and RNA templates, designed to aid exam preparation.

RNA-dependent RNA polymerase (RdRp)

Enzyme that copies RNA templates into RNA; essential for RNA virus replication and transcription; often packaged with certain genomes and contains conserved motifs A–E.

Positive-sense RNA

Genomic RNA that can function directly as mRNA and be translated by host ribosomes; infectious when deproteinized for some viruses; still requires RdRp for genome replication.

Negative-sense RNA

Genomic RNA that cannot be directly translated; must be copied to a positive-sense template by RdRp to produce viral proteins; often packaged with RdRp and nucleoproteins.

Ambisense genome

Genome with both positive- and negative-sense regions; replication/transcription involve an antigenome intermediate and distinct synthesis steps.

Nucleocapsid (N) protein

RNA-binding protein that forms nucleocapsids with negative-sense genomes; protects RNA, maintains single-strandedness, and aids replication by regulating access to the template.

Cap snatching

Influenza strategy of stealing 5′ capped ends from host mRNAs to prime viral mRNA synthesis; involves cap-binding and endonuclease activities.

Conserved 11-nucleotide segment (Influenza)

A short, conserved sequence at the 5′ end of each influenza genome segment that helps activate cap snatching and replication machinery.

Poly(A) tail addition

Most RNA virus mRNAs end with a poly(A) tail; added by mechanisms like reiterative copying in negative-strand viruses (e.g., VSV) or moving-template poly(A) addition in influenza; arenaviruses/reoviruses may differ.

RNA interference motifs (A–E) in RdRp

Common sequence motifs in RdRps; motifs A and B bind/recognize nucleotides, motif C contains a critical glycine-aspartic acid-aspartic acid sequence, motif D helps form the palm, and motif E is unique to RdRps and binds primers.

Motif C (RdRp)

Conserved motif in RdRp containing glycine-aspartic acid-aspartic acid; serves as a key indicator of RdRp identity and catalytic activity.

De novo initiation vs primer-dependent initiation

RdRps may initiate RNA synthesis without a primer (de novo) or require a primer (protein-linked or capped) to begin synthesis.

VPg (virus protein genome-linked primer)

Protein primer used by poliovirus to initiate RNA synthesis; VPg is uridylylated to form VPg-pUpU and acts as a primer.

Cis-acting replication element (cre)

Internal RNA sequence in poliovirus genome recognized by 3CDpro; templates primer formation with VPg and guides replication.

3AB-3CD

Viral proteins that bind to the 3′ noncoding region and recruit RdRp to the replication complex in poliovirus.

Primer-primed RNA synthesis (protein-priming)

RdRps initiate synthesis using a primer that is protein-linked (e.g., VPg) rather than a free 3′-OH primer.

Cap-binding complex activation in influenza

Influenza endonuclease-primed cap-snatching requires coordinated binding of 5′ ends and segment termini to activate primer synthesis.

PABP (poly(A)-binding protein) in RNA synthesis

Host protein that binds poly(A) tails and interacts with viral factors (e.g., poliovirus complex) to circularize RNA and promote synthesis.

PCbp (poly rC-binding protein)

Host protein that binds cloverleaf RNA and cooperates with viral 3CDpro to initiate (-) strand synthesis in poliovirus.

3CDpro

Viral protease that participates in replication complex formation and primer recruitment (e.g., with VPg and cre in poliovirus).

Cloverleaf RNA structure

5′ end RNA structure in poliovirus that binds PCbp and 3CDpro to form replication complexes.

PAbp1

Poly(A)-binding protein that interacts with the poliovirus replication complex and the 3′ poly(A) tail to promote RNA synthesis.

Poly(A) tail synthesis by polymerase stuttering

Mechanism where RdRp adds a poly(A) tail by repeatedly stuttering on a short U tail in negative-strand templates (e.g., VSV).

Moving template model of poly(A) addition (Influenza)

Model in which the nascent RNA is anchored at the 5′ end while synthesis proceeds, causing poly(A) tail addition via template slippage.

Sindbis virus nsP1–nsP4

Non-structural polyproteins that are cleaved to form the RdRp complex; sequential cleavage changes polymerase specificity during replication.

Sequential cleavage of RdRp (Sindbis)

Cleavage events alter polymerase activity, switching from negative-strand synthesis to full-length genome synthesis and ultimately to subgenomic RNA synthesis.

Reassortment

Exchange of whole genome segments between co-infecting segmented viruses, generating new genotypes; common in influenza and a major source of antigenic shift.

Antigenic shift

Major genetic shift due to reassortment of segmented genomes, leading to new viral strains and potential pandemics (e.g., influenza A).

Antigenic drift

Gradual accumulation of mutations in viral surface proteins (e.g., influenza HA/NA) causing epidemics.

Recombination

Exchange of genetic material between RNA genomes; can be nonreplicative (end-joining) or replicative (template switching) and increases diversity.

RNA editing

Insertion or modification of nucleotides in viral RNA to diversify genomes (e.g., measles, Ebola); adds or alters coding potential.

L protein and P protein (VSV)

L is the catalytic subunit; P acts as a cofactor bridging genome-N complex to L polymerase; essential for transcription/replication in vesicular stomatitis virus.

Rotavirus (dsRNA) replication inside capsid

Double-stranded RNA genome replicated within the virion capsid; positive-strand RNA serves as template for synthesis, then forms dsRNA in progeny virions.

Ambisense replication (bunyaviruses/arenaviruses)

Replication involves transcription from both genome and antigenome with internal RNA structures; require antigenome for full replication.

Pseudoknot structure

Complex RNA secondary structure involved in replication control and interactions with nucleoproteins and polymerases.

Nucleoprotein-RNA complexes in negative-sense viruses

Nucleoprotein coats RNA within nucleocapsids, protecting RNA, preventing secondary structure formation, and coordinating replication with RdRp.

RNA secondary structures in replication

Stem-loops, hairpins, bulges, interior loops, and pseudoknots that influence replication and transcription efficiency.

Influenza genome organization

Influenza is an enveloped Orthomyxoviridae virus with eight segmented, negative-sense RNA genomes packaged with polymerase and NP.

Influenza antigenic shift vs drift (examples)

Shift leads to pandemics via reassortment; drift leads to seasonal epidemics via gradual mutations in HA/NA.

Replication compartmentalization (examples)

Separation of RNA synthesis and translation in time or space (e.g., poliovirus temporal separation; reovirus compartmentalization in capsid).