LOs: 11-12 Flashcards
11 Nonenveloped vs. Enveloped Viruses
Nonenveloped
- Nucleocapsid = viral genome enclosed within a capsid
- Neutralizing antibodies recognize capsid proteins
Enveloped
- Nucleocapsid surrounded by a lipid-containing envelope
- Neutralizing antibodies recognize outer envelope proteins
11 Baltimore Classification System
DNA
- dsDNA
- ssDNA
RNA
- dsRNA
- ssRNA: (+) strand (Retroviruses) or (-) strand
11 DNA Viruses:
Enveloped Families
Nonenveloped Families
ssDNA vs. dsDNA
Linear vs. Circular
Helical vs. Icosahedral
Nucleus vs. Cytoplasm Replication
Hepadna
Herpes
Irido
Pox
Parvo
Papova
Adeno
All dsDNA except parvo
All linear except papova & hepadna
All icosahedral except pox
All nucleus except pox
11 RNA Viruses:
Enveloped Families
Nonenveloped Families
Segmented
ssRNA vs. dsRNA
Nucleus vs. Cytoplasm Replication
“gRhab Are Buny Filo ROP Tog(et)a Corona Flavi”
Rhabdo Arena* Bunya* Filo Retro Orthomyxo* Paramyxo Toga Corona Flavi
“PiCaReo”
Picorna
Calci
Reo*
*Segmented
All ssRNA except reo
All cytoplasm except orthomyxo & retro
11 Virus Life Cycle
Initiation Phase
Replication Phase
Release Phase
Initiation Phase
- Attachment: protein on virion surface binds to a cell surface protein (viral receptor)
- Penetration: viral particle or nucleocapsid moves through the plasma membrane via fusion (enveloped) or receptor-mediated endocytosis (either)
- Uncoating: release of viral genome from capsid
Replication Phase
- Gene Expression: viral protein synthesis
- Genome Replication: nucleic acid synthesis
Release Phase
- Assembly: capsid + genome + virion-associated proteins in inclusion bodies
- Release/Egress: move to cell surface & release infectious virus particles by budding or fusion
- All enveloped viruses derive envelopes from cell membrane
- Death of cell may or may not occur
- Nonenveloped viruses usually exit by lysis
- New round of infection & virus replication
11 Virus Replication Stratgies
Encode their own replication enzymes: viral polymerases (except parvo, only ssDNA)
DNA viruses replicate in nucleus (except pox)
RNA viruses replicate in cytoplasm (except influenza/orthomyxo)
High mutation rate (error prone) for immune evasion & drug resistance
11 DNA Virus Replication:
Encode own viral DNA polymerase?
Viral DNA vs. host DNA replication
Targets of antiviral therapy
Requirements for infectivity
Early vs. Late viral proteins
Large DNA viruses
No, except parvo (only ssDNA)
Viral DNA polymerase is more efficient than host DNA polymerase at replicating viral DNA
Viral polymerases
Only the viral DNA genome (cellular machinery makes all necessary proteins from DNA)
Early: made prior to DNA replication,important for altering host cell & for viral genome replication
Late: made after DNA replication, important for virus structure & assembly
Ex. herpesviruses
- Immediate early proteins: for expression of early & late genes
- Early genes: for viral DNA replication
- Late genes: encode structural proteins
11 (+) RNA Virus Replication:
Viral RNA genome
Viral RNA polymerase
Viral (+) RNA
Steps (3)
Brought in w/ virus, can function as mRNA to encode viral proteins using host cell translation machinery
Makes complementary copies of the viral genome used for translation of viral proteins
Packaged into new virus particles to generate new infectious virus
(1) Translation of virion RNA as mRNA using host cell machinery
(2) Synthesis of +RNA & -RNA by RdRp
(3) Assembly of structural proteins & +RNA to generate progeny virions
11 (-) RNA Virus Replication:
Encode own viral RNA polymerase?
Viral (+) RNA
RNA polymerase
Steps (4)
No, require a packaged RNA polymerase
- (-) RNA is converted to (+) RNA using RNA polymerase brought into the cell as part of the virus particle
Translated by host cell machinery to make capsid, envelope, RNA polymerase, & other viral proteins
Makes (-) RNA which is packaged into virus particles along RNA polymerase to generate new infectious virus
(1) Synthesis of +RNA using RNA polymerase brought in w/ virus particle
(2) Translation of mRNA to make viral proteins
(3) Synthesis of -RNA by RdRp
(4) Assembly of structural proteins, -RNA & RdRp are packaged to generate progeny virions
11 Retrovirus Replication:
(+) RNA
Integration
Viral mRNAs
Viral RNA
Steps (4)
Converted to dsDNA using reverse transcriptase (RT) brought into the cell as part of the virus particle
Integrase brought into the cell as part of the virus particle integrates the viral dsDNA genome into host cell DNA to generate the provirus
Made from the provirus genome using the host cell machinery, translated by the host cell machinery to make capsid, envelope, RT, protease and integrase plus other viral proteins
Packaged into new virus particles along with RT, integrase and protease to generate new infectious virus
(1) RNA/DNA synthesized using reverse transcriptase brought in w/ virus
(2) dsDNA synthesized by RT & integrated into host cell DNA using viral integrase brought in w/ virus particle
(3) Replication, transcription, & translation
(4) Assembly of structural proteins, packaged to generate progeny virions
11 Hepatitis B Virus Replication:
Virus family
ss/ds DNA/RNA
Unique aspect
Steps (4)
Hepadnavirus
Incompletely dsDNA
Uses reverse transcriptase for replication
(1) Gapped DNA repaired in nucleus
(2) Viral mRNA & pregenomic RNA made using host cell machinery
(3) Pregenomic RNA is exported to cytoplasm to be a template for RT to form dsDNA w/ newly formed viral particles
(4) Particle is released from cell or directed back to nucleus
12 Stages in Viral Pathogenesis (6)
Entry
- How does the virus get into the body?
- What route (respiratory, fecal-oral, via the skin like a puncture wound, via the blood, STI, etc.)
- Affects where the virus then spreads
- Where could you block the infection by blocking entry? (Ex. barrier methods for STIs)
Primary Replication
- Where does primary replication occur?
- What cells does it replicate in?
- Can the virus attach to and enter cells? (Need specific receptors)
Primary Viremia (spread through bloodstream)
- How does the virus spread through the body?
- Some will stay localized, others will spread
- Common route: via bloodstream
- When get virus into blood, get systemic infection
Secondary Replication
- How does the host respond to block infection or clear virus-infected cells? (Innate vs. Adaptive Immunity)
- How does the virus infect & damage cells?
- Cells need virus receptors on their surface
Spread to Target Organs
- What organs/tissues are infected?
Further Replication, Cell Injury, & Clinical Disease
- How is the infection transmitted to other hosts?
12 Viral Dissemination:
Routes (3)
Factors affecting dissemination (3)
(1) Hematogenous spread (viremia)
(2) Localized spread (rhinoviruses, papillomaviruses)
(3) Neural spread (rabies, HSV, VZV, arboviruses)
(1) Portal of entry (blood, placenta, respiratory tract, GI tract, skin, STI)
(2) Host immunity (innate & adaptive responses)
(3) Cell-specific virus receptors (for virus to enter cell)
12 Viral Tropism:
Factors affecting it
Examples:
HIV-1
Influenza
Poliovirus
(1) Proteins on cell surface (viral receptor)
(2) Proteins on virus surface (interacts w/ cell surface receptor)
HIV-1
Receptor: CD4
Co-Receptor: CCR5, CXCR4
Influenza
Receptor: Sialic Acid
Co-Receptor: CLRs (CD209, CD209L, MMR)
HIV-1
Receptor: Pyr (CD155)
12 Possible cellular outcomes of viral infection (4)
Lysis of infected cell
No morphological or deleterious change (persistent or chronic infections)
Cell dysfunction or morphological changes
- Hyperplasia
- Excessive mucous secretion
- Syncytia formation (fusion of cells to form multinucleated giant cells)
Transformation into an immortalized phenotype (cancer)
