Viral pathogens: classification, biology, diseases I Flashcards

1
Q

What is a virus?

A
  • An infective agent that typically consists of a nucleic acid molecule in a protein coat, is too small to be seen by light microscopy, and is able to multiply only within the living cells of a host
  • Viruses aren’t alive - molecular machines that wish to replicate
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2
Q

State the differences between virus, bacteria and prions?

A
  • Bacteria contain nucleic acid (DNA) covered in protein, have a polysaccharide cell wall (a coat of sugar molecules) and can replicate outside of the cell.
  • Remember viruses can be found within bacteria
  • Prions are proteins, do not contain nuclei acid and replicate inside the cell.
  • Viruses are nucleic acid (DNA or RNA) covered by proteins, have no cell wall and may or may not have a lipid coat. Viruses must replicate in the cell; they are “obligate cellular parasites”
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3
Q

State the similarities between virus, bacteria and prions?

A

Similarity is that they all are infectious and too small to be seen under a microscope

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4
Q

Why are viruses described as obligate cellular parasites?

A
  • OCP require a host cell to live and reproduce - they cannot reproduce outside their host cell. Same way viral proteins are formed and exist
  • The reproduction of the virus is entriely reliant on intracellular resources of the host
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5
Q

What are the essential structural features of a virus? VD

A
  • Different viruses have different structures - but retain similar organisation
  • The structure dictates host range (organisms or place where virus is found) and tissue tropism (tissue where virus is found)
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6
Q

State the different types of configurations/structure of viral genomes? (PART 1)

A
  • Single-stranded RNA (SSRNA)
  • Double-stranded RNA (dsRNA)
  • Single-stranded DNA (SSDNA)
  • Double-stranded RNA (dsDNA)
  • Double-stranded genomes have complementary base pairing
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7
Q

State the different types of configurations/structure of viral genomes? (PART 2)

A
  • RNA genomes can be linear and segmented i.e. more than one RNA per capsid
  • Segmented where the genome is fragmented into 2 or more nucleic acid molecules
  • DNA genomes can be linear or circular.
  • Genomes can be encode information (genes) in positive or negative sense; 5’-3’ or 3’-5’ respectively.
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8
Q

What is the central dogma?

A

The ‘Central Dogma’ is the process by which the instructions in DNA are converted into a functional product - protein

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9
Q

How do viruses use it?

A
  • (-) sense RNA Is a template strand tor mRNA - complementary to mRNA, but can’t be directly translated
  • Is reverse complementary to both the positive-sense strand and the
    RNA transcript. It is actually the antisense strand that is used as the template from which RNA polymerases construct the RNA transcript,
  • (+) sense RNA is produced from - sense RNA (complementary to tis) via
    RdRp as its sequences signifies of a particular viral mRNA sequence, so can be directly translated into viral proteins
  • if its nucleotide sequence corresponds directly to the sequence of an RNA transcript which is translated or translatable into a sequence of amino acids
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10
Q

What is baltimore classification?

A

System used to classify viruses based on the structure of the genome and how this used is used to produce mRNA.

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11
Q

What are the essential features of virus replication?

A
  • Entry into the cell - attachment/entry receptors - direct fusion or endocytosis.
  • Genome movement within the cell - intracellular structures.
  • Genome replication
  • Genome packaging into protein shells - “Packaging” sequences in viral DNA or RNA.
  • Exit from the cell - budding or lysis -> New virus is formed
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12
Q

Describe the molecular structure of HIV particle?

A
  • Outer envelope + core
  • Core: 2 (+) RNA strands, tRNA^Lys3, + ~50 copies of viral enzymes - protease, reverse transcriptase + integrase -> surrounded by nucleocapsid (coats viral RNA genome, capsid (conical capsid formation) + matrix associates with membrane (in order)
  • OE -> Lipid bilayer + protuding Envelope spikes (surface OR transmembrane)
  • Envelope -> shells of Gag proteins
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13
Q

State what polyproteins are synthesised by HIV retroviruses which go on to form the required proteins for HIV formation?

A
  • Gag -> Group specific antigen -> Forms viral core proteins -> MA, CA + NC
  • Pol -> viral enzymes -> PR, RT, IN
  • Env -> Envelope glycoprotein -> gp120 SU OR gp41 TM spikes
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14
Q

State and describe the function of HIV-1 regulatory/accessory proteins in the HIV genome structure?

A
  • Tat: Potent activator of viral transcription
  • Rev: Mediates unspliced RNA nuclear export
  • Vif: Critical regulator of virus infectivity
  • Nef: Immune modulator, T-cell activation, virus spread (?)
  • Vpu: Immune modulator, virus release
  • Vpr: Cell cycle, virus nuclear import (?)
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15
Q

What are the 2 elements found on HIV RNA and 1 on HIV DNA known as?

A
  • HIV RNA - Trans-activation response element (5’ end) + Rev response element (3’ end)
  • HIV DNA - Long terminal repeat
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16
Q

How do viral proteins enter the cell?

A

Entry: Viral envelope proteins with cellular receptor attaches to cell + fuse into cell cytoplasm

17
Q

Describe the composition of HIV-1 Env + roles in HIV-1 entry?

A
  • Trimer of gp41 (TM) + gp120 (SU) -> covered with glycans
  • Tm - Mediates fusion of viral envelope
  • SU -> Cell surface receptor recognition
18
Q

What does HIV-1 entry require and what HIV tropic for - what can this lead to?

A
  • 2 membrane proteins - CD4 + chemokine receptor (CCR5/CXCR4)
  • Tropic for -> CD4 expressing cells (Th OR macrophages) - loss = immunodefiency (+ AIDS)
19
Q

Describe the process of HIV-1 entry?

A
  • Native trimer: looking for cell with CD4 receptor ->
  • CD4 binding (T20 binding site exposure): CD4 binds - conformational changes - open trimer formation - uncovers TM subunit - interaction of lipid + TM ->
  • CoR binding to membrane - fusion peptide inserted ->
  • 6-helix bundle formation - membrane fusion
20
Q

Describe the phases after entry of HIV-1 until into nucleus?

A

Viruses fuses + deposits core (containing viral genome) into cell ->
- Uncoats + undergoes RT ->
- Microtubule network moves core towards nuclear membrane for replication

21
Q

Describe reverse transcriptase in terms of subunits and its 3 enzymatic activities?

A
  • Heterodimer of p66 (catalytic) + p55 subunit (structural + lacks RNAse H domain)
  • EA -> RNA-dependent DNA polymerase, RNAase H (cleaves RNA from RNA/DNA hybrid), DNA-dependent DNA polymerase
22
Q

Describe the basic steps of reverse transcriptase?

A
  • RNA genome bound by RNA primer ->
  • RT acts as polymerase ->
  • Converts to dsDNA ->
  • Inserted into viral genome + transported to nuclear membrane
23
Q

Describe how nuclear entry of HIV-1 occurs + how it could be prevented?

A
  • Nuclear pore -> requires nucleoporin Nup358 + Nup153 -> for optimal gene density -> mutation of capsid or impaired NP prevents
24
Q

Retroviral replication cycle - integration
How is the viral RNA + integrase targeted to the chromatin?

A

Preintegration complex (containing LEDGF/P75) binds I -> facilitates targetting
VD

25
Q

State the enzyme and the steps behind retroviral integration?

A
  • HIV DNA genome (provirus) integrated into host chromosome -> via integrase -> binds both host + viral DNA
  • Steps -> Provirus brought closely with cellular DNA -> | cuts CD + repairs -> binds both CD + VD -> I repairs cuts
26
Q

Describe the retroviral replication cycle within the nucleus?

A
  • HIV-1 promotor contains binding site for TF (present in T-lymphocytes) -> HIV produces Tat protein -> Tat binds TAR RNA within cell genome + increased elongation of RNA pol II († transcription of viral genes > cellular) -> HIV-1 provirus generates different mRNAs for viral proteins