LOs: 11-12 Flashcards Preview

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Flashcards in LOs: 11-12 Deck (21):
1

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

2

11 Baltimore Classification System

DNA
- dsDNA
- ssDNA

RNA
- dsRNA
- ssRNA: (+) strand (Retroviruses) or (-) strand

3

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

4

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

5

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

6

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

7

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

8

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

9

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

10

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

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

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?

13

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)

14

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)

15

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)

16

12 Patterns of Viral Infection in the Host (4)

Acute Infection / Death
- POLIOVIRUS, Ebola, Hantavirus

Acute Infection / Clearance
- INFLUENZA VIRUS, POLIOVIRUS, Rhinovirus, Rotavirus
- Host can amount a decent immune response to clear the virus

Persistent Chronic Infection
- HIV, Hepatitis B & C

Latent Infection & Reactivation
- HIV, HSV, EBV, VZV, CMV
- Replicate, disappear, reappear

17

12 Poliovirus Pathogenesis (7)

Entry via GI tract (fecal-oral)

Withstand acid environment

Primary replication in mesenteric lymph nodes in small intestine

Excreted in stool

Spread through bloodstream

Replication in liver & spleen

Spread to CNS (rare)
- Meningitis, encephalitis (headache, fever, self-limiting)
- Paralytic poliomyelitis (flaccid paralysis)
- Post polio syndrome (rare, paralysis & muscle wasting)

18

12 Latent vs. Chronic Persistent Infections

Part of virus life cycle, strategy for survival

No production of infectious virus

Potential to undergo reactivation
- Enters replicative cycle & produces infectious virus in response to stress, cellulary injury, or permissive cell types

19

12 Mechanisms of Viral Mutation (3)

Point Mutations
- RNA viruses: error-prone RNA polymerase, lacks proofreading
- DNA viruses: less accurate proofreading

Recombination of homologous nucleic acid sequences

Reassortment
- Occurs in viruses w/ segmented RNA genomes (ex. influenza)
- Swapping segments b/n 2 different viruses that infect the same cell

20

12 Antigenic Shift vs. Antigenic Drift

Antigenic Shift – sudden dramatic shift in viral antigen due to reassortment.

Antigenic Drift – more subtle change in viral antigens due to point mutations.

21

12 How HIV Evades Immune Surveillance (4)

Latency: Minimal to no expression of viral antigens.

Antigenic variation: virus rapidly evolves and
mutates antigenic sites that are critical for immune recognition

Viral “defense” molecules that interfere with immune
function, such as antigen processing and presentation

Infection of immune cells with destruction or
alteration of immune cell function