Quiz 4: Virology

Lectures 06 & 07 (9/17 & 9/22)

Central Dogma of Molecular Biology

Genetic information flows from DNA → RNA → protein. DNA and RNA synthesis require complementary templates, while proteins are synthesized by ribosomes using RNA as a template

DNA replication

Synthesis of DNA from a DNA template using DNA polymerase (DdDp); in eukaryotic cells, this normally occurs in the nucleus.

Transcription

Synthesis of RNA using RNA polymerase (DdRp); in eukaryotic cells, this occurs in the nucleus.

Translation

Synthesis of protein from an mRNA template by ribosomes; occurs in the cytoplasm or ER.

mRNA processing

Nuclear processing of mRNA that includes 5′ methylation, splicing, and polyadenylation.

Ribonucleotide

Building block of RNA consisting of a phosphate group, ribose sugar, and nitrogenous base.

Deoxyribonucleotide

Building block of DNA consisting of a phosphate group, deoxyribose sugar, and nitrogenous base.

DNA base pairing

Complementary DNA bases pair as G ↔ C and A ↔ T.

RNA base pairing

During RNA synthesis, complementary bases pair as G ↔ C and A ↔ U.

Hydrogen bonds

Bonds that hold complementary nitrogenous bases together between the two DNA strands.

DNA polarity

The chemical difference between the 5′ and 3′ ends of a DNA strand, giving the strand directionality.

5′ end

End of a nucleic acid strand with a free phosphate group attached to the 5′ carbon of the sugar.

3′ end

End of a nucleic acid strand with a free hydroxyl (–OH) group attached to the 3′ carbon of the sugar.

Antiparallel DNA

The two complementary strands of a DNA double helix run in opposite orientations.

5′ → 3′ synthesis

DNA and other nucleic acids are synthesized specifically in the 5′ → 3′ direction.

Complementary template

A nucleic acid strand used to direct synthesis of another strand according to base-pairing rules.

Sense strand (+)

DNA strand that is not used as the transcription template and has the same sequence as the resulting mRNA except DNA has T instead of U.

Antisense strand (−)

DNA strand that serves as the template for transcription; it is complementary to the resulting mRNA.

Sense/antisense relativity

Whether a DNA strand is sense or antisense is relative to a particular gene/ORF; the same DNA strand can be sense for one gene and antisense for another.

Gene orientation

Genes in dsDNA can be encoded in either direction, meaning either DNA strand can serve as the antisense/template strand depending on the gene.

Template-directed polymerase

An enzyme that copies nucleic acids by using another nucleic acid strand as a template.

DNA-directed DNA polymerase (DdDp)

Uses DNA as the template → synthesizes DNA.

RNA-directed DNA polymerase (RdDp)

Uses RNA as the template → synthesizes DNA; also called reverse transcriptase (RT).

DNA-directed RNA polymerase (DdRp)

Uses DNA as the template → synthesizes RNA.

RNA-directed RNA polymerase (RdRp)

Uses RNA as the template → synthesizes RNA.

Reverse transcriptase (RT)

Another name for RdDp; synthesizes DNA using an RNA template.

Host-cell polymerases

Host cells contain DdDp and DdRp for DNA replication and RNA synthesis, respectively.

RNA-directed polymerases in host cells

Host cells do not typically contain RdDp or RdRp; therefore, viruses requiring them must encode their own.

Viral polymerase dependence

Some viruses use host DdDp/DdRp, while others encode their own polymerases.

Polyomaviruses / Papillomaviruses

Small circular dsDNA viruses that do not encode their own DNA polymerase and therefore depend on host-cell polymerases.

Adenoviruses

Linear dsDNA viruses that encode their own DNA polymerase (DdDp).

Herpesviruses

Linear dsDNA viruses that use a combination of host and viral polymerases.

Poxviruses

Linear dsDNA viruses that encode their own polymerases and replicate their DNA in the cytoplasm rather than the nucleus.

Early viral genes

Viral genes expressed early in infection, generally producing proteins needed to modify the host cell and/or enable viral genome replication.

Late viral genes

Viral genes expressed later in infection that include genes encoding virion structural proteins.

Viral structural proteins

Proteins produced during late gene expression that become components of newly assembled virions, such as capsid proteins.

Egress

Release of newly produced viral particles from the infected cell.

dsDNA viruses without their own DdDp

Small dsDNA viruses that rely on host-cell DNA polymerase to replicate their viral DNA.

Host cell-cycle stimulation

Early viral proteins modify host-cell cycle control to stimulate cellular DNA replication, making host DNA polymerase available for viral genome replication.

Early transcription – polyoma/papilloma

Cellular RNA polymerase transcribes the virus's early genes after the circular viral genome reaches the nucleus.

Genome replication – polyoma/papilloma

After the host replication machinery is stimulated, viral DNA is replicated by host-cell DNA polymerase.

Late transcription – polyoma/papilloma

Cellular RNA polymerase transcribes late viral genes encoding virion structural proteins such as capsid proteins.

Assembly – polyoma/papilloma

Newly produced viral particles are assembled in the nucleus.

Adenovirus genome entry

The linear dsDNA genome is delivered into the nucleus following attachment and entry.

Adenovirus early genes

Host-cell RNA polymerase transcribes early viral genes, including the gene encoding the virus's DNA polymerase.

Adenovirus immune antagonism

Host RNA polymerase transcribes specific viral RNAs that antagonize interferon/innate immunity.

Adenovirus cell-cycle manipulation

Early viral gene products override cell-cycle controls and inhibit apoptosis.

Adenovirus DdDp

Viral DNA polymerase produced from an early gene that performs viral genome replication.

Adenovirus late genes

Genes transcribed by host RNA polymerase II from a single major late promoter, including genes for viral structural proteins.

Adenovirus assembly

Newly produced virions are assembled in the nucleus, then leave the nucleus, traffic to the cell surface, and undergo egress.

Herpesvirus genome circularization

The linear dsDNA genome enters the nucleus and circularizes.

Immediate-early α genes (herpesvirus)

First class of herpesvirus genes transcribed by cellular RNA polymerase.

α gene products (herpesvirus)

Include transcription factors that allow host RNA polymerase to recognize promoters for the viral β genes.

β genes

Herpesvirus genes encoding viral DNA polymerase, other genome-replication proteins, and transcription factors needed for γ-gene expression.

γ genes

Late herpesvirus genes that include genes encoding virion structural proteins.

Herpesvirus gene-expression cascade

Sequential viral gene expression: α → β → γ, with earlier gene products helping activate later gene classes.

Herpesvirus assembly

Virions assemble in the nucleus, bud out of it, traffic through the ER/Golgi, and are secreted.

Poxvirus replication location

Unlike the other dsDNA viruses discussed, poxviruses carry out replication in the cytoplasm.

Poxvirus viral core

After entry, the viral core enters the cytoplasm, where viral transcription begins.

Virion DdRp

Poxvirus DNA-dependent RNA polymerase carried in the virion that transcribes early viral genes.

Poxvirus early genes

Encode factors involved in releasing dsDNA into the cytoplasm, viral DNA polymerase, DNA-replication enzymes, and transcription factors.

Poxvirus intermediate genes

Genes whose products include transcription factors required for late gene expression.

Poxvirus late genes

Produce structural proteins, viral transcriptase, and associated factors needed for newly produced virions and the start of the next infection.

Poxvirus assembly and maturation

Following late gene expression, viral components undergo assembly and maturation, followed by egress.

Antigenome

Complementary strand to the viral genome that serves as a template for making new genomes.

Positive-sense ssRNA (+ssRNA)

RNA genome that can function directly as mRNA and be translated by host ribosomes.

Negative-sense ssRNA (-ssRNA)

RNA genome that must first be copied into +ssRNA before viral proteins can be made.

Double-stranded RNA (dsRNA)

RNA genome consisting of two complementary RNA strands.

+ssRNA antigenome

A −ssRNA strand complementary to a +ssRNA genome.

-ssRNA antigenome

A +ssRNA strand complementary to a −ssRNA genome.

Subgenomic RNA (sgRNA)

RNA corresponding to only part of the viral genome, such as a single gene, that functions as mRNA.

Viral genome replication

Production of new copies of the viral genome for packaging into progeny virions.

Viral mRNA synthesis

Production of viral mRNA that host ribosomes translate into viral proteins.

RNA synthesis direction

RNA is synthesized 5′ → 3′ using a template of opposite polarity.

Template polarity

The template strand has the opposite polarity from the RNA strand being synthesized.

+ssRNA incoming genome

Can immediately function as mRNA and can also serve as a template for making an antigenome.

-ssRNA incoming genome

Cannot be directly translated; it must first be copied into +RNA.

Virion RdRp

RdRp packaged within the virus particle so RNA synthesis can begin after infection.

Core-associated RdRp

dRp within a dsRNA viral core that transcribes the dsRNA genome into mRNA.

Replication compartment

Virus-established cellular location where viral RNA replication occurs.

Virus factory

Cytoplasmic region established by viral proteins where viral RNA synthesis and replication occur.

Structural proteins

Viral proteins that become physical components of progeny virions.

Nonstructural proteins

Viral proteins involved in processes such as genome replication rather than forming the virion.

Progeny genome

Newly synthesized viral genome that can be packaged into a new virion.

+ssRNA virus without subgenomic RNA

Uses its genomic RNA directly as mRNA to produce structural and nonstructural proteins.

+ssRNA virus with subgenomic RNA

Uses genomic RNA to produce nonstructural proteins and subgenomic mRNAs to produce structural proteins.

−ssRNA nuclear transcription

Orthomyxoviridae and Bornaviridae carry out transcription in the nucleus.

−ssRNA cytoplasmic transcription

Rhabdo-, Filo-, Paramyxo-, and Bunyaviridae carry out transcription in the cytoplasm.

Gene expression after viral entry

Viral mRNA must be produced so host ribosomes can synthesize viral proteins.

Genome replication after viral entry

New genome copies must be produced so each progeny virion can receive a genome.

Ambisense viruses (opt)

(opt) a type of single-stranded RNA virus that has protein instructions pointing in both positive and negative directions on the same strand of genetic material

Polyprotein precursor

a large, single protein translated from a viral or cellular messenger RNA that is later cleaved by enzymes into multiple smaller, functional mature proteins

interferons

Adenoviruses trigger rapid host innate immune responses via pattern recognition receptors that induce ____

• specialized signaling proteins released by infected cells that act as a primary defense line in the Innate Immunity system