Virus Structure and Replication Flashcards

1
Q

What is a Virus?

A
  • Obligate intracellular parasite
  • Small
    • submicroscopic “filterable” infectious agent
  • Possesses genetic material
    • DNA or RNA
    • ds or ss
  • Infectious to a variety of living organisms:
    • Humans, animals, plants, bacteria, invertebrates, fungus
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2
Q

What is the size of viruses?

A
  • 100 nm
    • vs bacteria at >300nm
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3
Q

What is special about Viral DNA/RNA?

A
  • Have DS DNA & RNA
  • Have SS DNA & RNA
  • vs Animals, plants, etc DS = DNA SS = RNA
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4
Q

How are viruses classified?

A
  • Originally classified by size
  • Then classified by pathogenic properties, transmission ecology, or organ tropism
    • Yellow fever, Hep A, B, &C, Rift valley fever would all be hepatitis viruses
  • NOW:
    • Order -virales
    • Family -viridae
    • Sub-family -virinae
    • Genus -virus
    • Species (Common Name) - viruses “share common features” (molecular/structural)
    • Isolate, strain, etc.
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5
Q

What are the types of viral genomes?

A
  • Composition: DNA or RNA
  • Form: SS or DS
    • Polarity of SS RNA:
      • Positive
      • Negative
      • Ambisense
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6
Q

How do viruses replicate?

A
  • Viral genomes MUST make mRNA that can be read by the host ribosomes
  • mRNA is (+)sense RNA
  • mRNA can be translated into a protein
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7
Q

What is Reverse Transcriptase?

A
  • Unique to retroviruses
  • Cells do NOT have a polymerase to turn RNA to DNA - A virus MUST bring its own
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8
Q

What are the Coding Regions of the Viral Genome?

A
  • Genes that produce proteins
  • Open Reading Frame (ORF):
    • has start codon
    • stop codon
    • intervening sequence that codes for a polypeptide of at least 100 amino acids
      • Non-structural proteins
      • Structural Proteins
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9
Q

What are the Non-coding regions of the Viral genome?

A
  • Normally referred to as “untranslated regions” (UTRs)
  • Contain:
    • Regulatory elements
    • Scaffolding
    • Terminal repeats
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10
Q

What are Non-structural Viral Proteins?

A
  • Participate in processes important to the virus
    • Viral replication
    • Regulating gene expression
    • Replication of the genome
    • Facilitating the assembly of the virus particle
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11
Q

What are viral structural proteins?

A
  • Components of the virion
    • envelope proteins
    • matrix proteins
    • capsid proteins
    • additional virion-associated proteins
    • provide receptor-binding sites
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12
Q

What information is contained in the viral genome?

A
  • Replication
  • Assembly and packaging
  • Regulation of the replication cycle
  • Modulation of host defense
  • Spread
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13
Q

What information is NOT contained in the Viral Genome?

A
  • Complete protein synthesis
  • Membrane synthesis
  • Energy production
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14
Q

What is a capsid?

A
  • The protein shell surrounding the nucleic acid genome
  • Self-assembled into a “minimum structure, maximal space” to stably package the genome
  • 2 Main types of capsid structures
    • Symmetrical
      • icosahedral and helical
    • Complex
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15
Q

What do Symmetrical Capsids look like?

A
  • Icosahedral
    • EX: Parvoviruses
      • 20 equilateral triangles
      • Made up of 60 identical copies of the capsid protein
  • Helical:
    • Cylindrical structure
    • Capsomeres arranged in a spiral staircase with a central pole as the axis
    • EX: Rhabovirus (Rabies)
      • Coiled helical nucleocapsid with a bullet shaped virion morphology
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16
Q

What does a complex capsid look like?

A
  • Not helical or icosahedral
  • Possess no symmetry
  • EX:
    • Filoviridae
    • Poxviridae
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17
Q

What is the function of the Capsid?

A
  • Genome Packaging
  • Host cell attachment and entry- (non-enveloped viruses)
  • Un-packaging of the genome and release into cells
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18
Q

What is a Nucleocapsid?

A
  • The complete protein-nucleic acid complex that is the packaged from of the genome in a virus particle
    *
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19
Q

What is the structure of Nucleocapsids?

A
  • Helical capsids
    *
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20
Q

What Families of Viruses have Helical capsids and (-)ssRNA genomes

A
  • Paramyxoviridae (bovine parainfluenza virus 3)
  • Rhabdoviridae (rabies)
  • Orthomyxoviridae (Influenze A)
  • Filoviridae (Marburg and Ebola)
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21
Q

What are the contents of Enveloped Viruses?

A
  • Lipid Envelope
  • Capsid
  • Genome
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22
Q

What are the contents of Non-enveloped Viruses?

A
  • Capsid
  • Genome
23
Q

How is a viral envelope created?

A
  • Lipid bilayer is derived or “stolen” from the host cell membrane because the viral genome does not have the machinery to encode a lipid bilayer
  • Stolen from:
    • Nuclear membrane
    • Endoplasmic reticulum (ER)
    • Golgi
    • Plasma membrane
24
Q

What are the functions of the Viral envelope?

A
  • Membrane glycoproteins - Antigenic sites, attachment, fusion
  • Protects the nucleocapsid - the capsid with the viral nucleotides
  • Facilitates direct transmission of virions to adjacent cells (cell-to-cell spread)
  • Camouflage- (surrounded by host cell material)
25
Q

Are Enveloped viruses stable?

A
  • Enveloped viruses are often more unstable than non-enveloped viruses
26
Q

What is E protein?

A
  • Major structural protein on the surface of mature flavivirus virion
  • Each E monomer consists of:
    • Domain 1 (red)
    • Domain II (yellow)
    • Domain III (blue)
27
Q

Are viruses alive?

A
  • Viruses are NOT alive
    • Do Not reproduce
    • Do Not evolve
    • Do Not metabolize…..
      • Without first infecting a cell
28
Q

What is a Virion?

A

The entire virus particle

29
Q

What is a virus particle?

A

A structure that has evolved to transfer nucleic acid from one cell to another

30
Q

How are Viruses classified?

A
  • Viral genome characteristics and nucleotide sequence
  • Capsid symmetry
  • Enveloped and non-enveloped
31
Q

What are the types of viral genomes?

A
  • Composition: RNA, DNA
  • From: single or double stranded
  • Polarity: for ssRNA - Positive or Negative
  • Presence of Reverse transcriptase (RT)
32
Q

What is the Viral envelope made of?

A
  • Lipid bilayer from the host cell
  • Has Viral envelope Glycoproteins
    • “spikes”
    • Specific to the virus
33
Q

How many different viral genomes are there?

A
  • Double stranded (dsDNA)
  • Single stranded (ssDNA)
  • Double stranded (dsRNA)
  • single stranded positive (ss+RNA)
  • single stranded negative RNA (ss-RNA)
  • single stranded positive RNA with a DNA step
34
Q

What are the requirements of the virus?

A
  • Attachment to the host cell
  • Penetration
  • Uncoating of the viral genome
  • Replication of the viral genome
  • Assembly of a new virion
  • Exit the host cell
  • Transmission to another host or cell
35
Q

What are the steps for viral replication?

A
  1. Receptor mediated
  2. Attachment and Entry
  3. Uncoating
  4. Genome replications
  5. RNA and Protein synthesis
  6. Assembly of nucleocapsid and maturation
  7. Release from the cell
36
Q

What is Reverse Transcriptase?

A

RNA-dependent DNA Polymerase

37
Q

What types of cells can a virus enter and replicate in?

A
  • Susceptible: has a receptor for a virus
  • Resistant: does not have the receptor for a virus
  • Permissive: can replicate the virus
  • Susceptible & Permissive: the virus can enter the cell and replicate
38
Q

What are the Steps for attachment and entry in Viral Replication?

A
  • Virions have to diffuse across the plasma membrane and then release the genome
  • Step:
    • Adhere to the cell surface
      • Not specific, happens by chance
    • Attach to a receptor
      • specific receptors on the cell
        • Made for proteins that the cell normally needs
    • Genome is then transferred into the cell
39
Q

What are the mechanisms of virus entry?

A
  • Macropinocytosis
  • Cavsolin/lipid raft
  • Phagocytosis
  • IL-2
  • Clathrin-mediated endocytosis
40
Q

What is Viral Fusion?

A
  • Endosome and Envelop Protein bind
  • Change from a Dimer to a Trimer
  • Allows the nucleic acid to come out of the virus and is released into the cytoplasm
41
Q

What is uncoating?

A
  • Acidic condition in the endosome triggers changes in viral structural proteins resulting in uncoating and release of the viral genome
42
Q

What information does the viral genome contain?

A
  • Replication
  • Assembly and packaging
  • Regulation of the replication cycle
  • Modulation of host defense
  • Spread
43
Q

How are viral genes transcripted?

A
  • DNA genome viruses:
    • Host or virus DNA-dependent RNA polymerase generates viral mRNA
    • mRNA is translated into viral proteins using cellular machinery
  • RNA genome viruses:
    • Require a viral-encoded RNA-dependent RNA polymerase (RdRp) to make mRNA (and genomic RNA)
    • Virus must possess of synthesize RdRp
44
Q

How is viral mRNA translated to viral proteins?

A
  • Translate the mRNA into proteins
    • protein synthesis
  • Compare to cell mRNA
    • 5’ cap UTR AUG ORF Stopp UTR AAAAAA 3’
  • Ribosomes are needed for Transltion
  • tRNA also needed to add the correct the AA
  • Translation also needs:
    • Initiation proteins
    • Elongation proteins
    • Termination proteins
45
Q

How are viral proteins named?

A
  • Named based on timing of synthesis
    • Early translation products
      • “immediate early” or “early”
      • mostly nonstructural proteins (polymerases, regulatory proteins)
    • Late translation products
      • “late proteins”
      • Structural proteins (capsid proteins, envelope glycoproteins)
46
Q

What is Post translational modification of proteins?

A
  • Further processing of viral proteins
  • RNA viruses frequently synthesize polyproteins that are cleaved by viral proteases
  • The first cleavage is an autocleavage to release a protease, which cleaves other proteins
47
Q

What happens during assembly of nucleocapsids and virus maturation?

A
  • Self assembly of the capsid
    • Many viral proteins assemble on their own
  • Assisted assembly:
    • Some need scaffolds and chaperones from the cell to form the viral structure
  • All Viruses need to:
    • Form the protein shell from one or many viral proteins
    • Assemble the protein shell
    • Release the virion from the host cell
  • Some:
    • Acquire an envelope
    • Go through virion maturation
48
Q

How can viruses exit the cell?

A
  • Budding - Acquires membrane
  • Lysis - break the cell open and release the virion
  • Release virus without lysis (poliovirus)
  • Move from cell to cell without cell lysis
49
Q

How do dsDNA viruses replicate?

A
  • Replicate in the nucleus
  • Protein vhs - cuts up the host cell mRNA which blocks host cell defenses (cell cannot make protein from mRNA)
  • Protein VP16 - facilitates the transcription of herpesvirus RNA
50
Q

What types of mRNA are produced by dsDNA viruses?

A
  • 3 types:
    • a - immediate early
    • B - early
    • y - late
51
Q

What types of proteins are produced by dsDNA virus?

A
  • 3 types of proteins:
    • Immediate early
    • Early
    • Late
52
Q

How are +RNA viruses (ie coronavirus) replicated?

A
  • Replicates in the cytoplasm (NOT the host cell nucleus)
  • Buds in the ER/golgi
  • Only makes 8 viral proteins
53
Q

How are Retroviruses replicated?

A
  • Have a provirus step
  • Replicate in the nucleus for the DNA step
  • When the host cell divides the virus divides with it because of the provirus