Virology - Principles Ii

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Viral replication and expression
“Genomic” vs “anti-genomic”

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i) Quasi species
ii) Recombination
iii) Reassortment

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DNA viruses (both ss and ds):

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DNA → DNA
i) Many have circular genomes
ii) Replication in nucleus (except poxviruses)
iii) Require early translation for required proteins for replication

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DNA retroviruses:

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dsDNA → covalently closed circular (ccc) DNA → mRNA and pregenomic (pg) RNA → dsDNA
i) Genome is partially dsDNA
ii) Similar strategy to RNA retroviruses

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ds RNA viruses

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dsRNA → mRNA → –RNA + mRNA = dsRNA
i) Replication in cytoplasm
ii) Incoming virus particle only partially uncoated
(1) Remains intact and always associated with genomic RNA
iii) Activates enzymes which synthesize mRNA from each genome fragment

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Positive stranded (+) RNA viruses

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+RNA (mRNA) → –RNA → mRNA
i) Replication in cytoplasm
ii) Naked RNA infectious
iii) Can produce single genomic or sub-genomic mRNAs

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Negative stranded (–) RNA viruses:

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–RNA → virion complementary (vc)RNA → –RNA
i) Enveloped
ii) Helical nucleocapsid
(1) Remains intact and always associated with genomic RNA (like dsRNA viruses)
iii) Replication in cytoplasm (except influenza virus)
iv) Naked RNA not infectious
v) vcRNA is plus sense, but not translated

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Ambisense viruses

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i) –RNA → vcRNA → –RNA
ii) –RNA → vcRNA → mRNA
iii) mRNA synthesized from both genome and anti-genome
iv) Neither genome nor anti-genome serves as the mRNA
v) Delays synthesis of mRNA made from anti-genome
vi) Otherwise the same as –RNA viruses

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RNA retroviruses:

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ssRNA (mRNA) → dsDNA → RNA
i) Enveloped
ii) Virion contains reverse transcriptase (RT) and RNase
iii) Replication steps in both cytoplasm and nucleus

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Cell functions required for virus replication and expression - DNA Viruses

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Viruses have small genomes and thus cannot encode for all necessary functions

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Cell functions required for virus replication and expression - RNA Viruses

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i) Can use all of the cell’s machinery or can encode own polymerase (especially larger viruses)
ii) Almost all encode a protein for the recognition of the origin of DNA replication
iii) Effect on cell permissivity and host range

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Cell functions required for virus replication and expression - Translation

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i) Must encode at least RNA polymerase (since no cellular RNA-dependant RNA polymerase exists)
ii) RNA polymerase + proteins (viral and cell encoded) = RNA replicase complex
(1) Recognizes promoters in viral RNA as starting point for RNA synthesis

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Cell functions required for virus replication and expression

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i) mRNAs translated by cellular ribosomes
ii) Cellular mRNAs usually have polyadenylated cap
iii) Some viral mRNAs have no cap
iv) Long open reading frame (ORF) with intermittent stop codons
v) Early translation: enzymes
vi) Late translation: structural proteins and those needed for replication of the genome

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What are Long open reading frame (ORF) with intermittent stop codons

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(1) Individual proteins
(2) Polyprotein
(a) Read through by
(i) Insertion
(ii) Ribosomal frame-shifting
1. Slippery sequence
2. Structural feature (hairpin)
3. Can be altered by mutation

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How does a virus infect a cell?

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a) Receptors-dictate host range, tissue tropism, pathology
b) Penetration

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How does a virus infect a cell? Receptors-dictate host range, tissue tropism, pathology

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i) Primary (high affinity)
ii) Accessory-largely electrostatic
iii) Co-receptors

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How does a virus infect a cell? - How do non-enveloped viruses penetrate a cell?

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(1) Protein conformational change (pH mediated?)
(2) Internalization may be of
(a) Entire nucleocapsid
(b) Sub-viral particle
(c) Naked nucleic acid

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How does a virus infect a cell? - How do enveloped viruses penetrate a cell?

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(1) Activation of fusion protein
(2) Fusion with cellular membrane
(a) Plasma membrane
(b) Endosomal membrane
(i) Endocytosis through clathrin-coated vesicles

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What happens when a virus infects a cell?

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a) Eclipse and productive phases

b) Lytic

c) Latent-infection without replication (eg. herpes viruses)

d) Persistent-viral replication without obvious effect on cell (eg. HTLV 1, 2)

e) Chronic-lysis of many cells, but some survive to develop persistent infection (eg. HIV)

f) Transformation-deregulated cell cycle

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How can a virus lyse a cell?

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i) Active lysis
(1) Apoptosis-no inflammation
(2) Necrosis-inflammation

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Transformation-deregulated cell cycle (cancer)

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i) Immortality
ii) Oncogenesis (oncogene incorporation into viral genome)

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Degree of viral replication in the cell

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a) Permissive

b) Semi-permissive

c) Non-permissive

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Infectivity

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a) Infectious dose
b) Reproduction number

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Localized infections

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i) Upper respiratory tract → “colds”
ii) Lower respiratory tract (ie. bronchi and lung) → pneumonia
iii) Liver → hepatitis

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Systemic or generalized infection

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i) Entry of virion through epithelial surface → uptake by dendritic cells with limited replication
ii) Migration to regional lymph nodes → uptake by macrophages/monocytes
iii) Primary viremia (may have prodromal phase → malaise, fever)
iv) Delivery to:
(1) Reticuloendothelial system (liver, spleen, bone marrow) → high replication
(2) Other organs via monocytes
v) Secondary viremia → delivery to target organ

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what is permissive viral replication?

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When a cell or host is defined as permissive in virology, it refers to the fact that the virus is able to circumvent host defenses and is able to replicate. Usually this occurs when the virus has modulated one or several of the host cellular intrinsic defenses, and the host immune system. The permissive state of a host has now been determined to be the primary factor in determining whether a virus will cause pathological symptoms in a host

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what is semipermissive viral replication?

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parital replication

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what is nonpermissive viral replication?

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no replication (nonpermissive) of the vir

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what is eclipse phase?

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phase during which the virion has entered the cell and before progeny virus are made. NO INFECTIOUS VIRUS are present during this phase
period in which virus gains control of host synthetic machinery and produce components required to assemble into virus
defined as the period between addition of virus and the appearance of assembled virus progeny inside the cell

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zoonatic viruses are usually what kind of virus?

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negative RNA

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Positive RNA = ?

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mRNA

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dsRNA makes what?

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mRNA and -RNA

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what does ambisense make?

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a mix of -RNA and mRNA

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How does ambisense start

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always -RNA