Week 2: Basics of virology Flashcards
How are viruses replicated in the lab?
Cell culture
What are viruses classified as?
Obligate intracellular organisms
Lytic vs pathogenic
lysis= Cell death and release of the virus
latent = limited viral synthesis but no cell death
What is a capsid?
Protein shell
released from cell by lysis and capsids are environmentally stable
What is a naked virus?
Virus that only contains a capsid
Viruses that contain an envelope
have a host cell membrane around the capsid and are more environmentally labile
Viral membrane glycopeptides
helpful for strain identification and are targets for neutralizing Antibodies
Also, act in viral attaching for tropism
Determine virulence and host tropism
Describe a viral infection by steps
- Recognize cell for which it has tropism
- Attachment
- Penetration
- Uncoating
- Transcription
- Protein synthesis
- Replication
- Assembly
- Lysis & release (cell-to-cell release/movement across tight junctions for local spread)
Stages of viral infection replication
- Primary replication
- Systemic spread
- Secondary replication
Stages of viral infection
- Prodrome - before symptoms
- Disease
- Convalescence (period of getting better)
describe the immune reaction to viruses
Acute infection - after week 1 controlled by IgM
Chronic infection - cell-mediated immunity
Vaccinations for prevention
Describe the innate immune response to viruses
- Macrophages recognize viral RNA
- Release antiviral cytokines (INF-α, β which interfere with viral replication and increase expression of MHC-1)
- NK cells kill viral infected cells
- Complement enhances phagocytosis
Describe the adaptive immune response to viruses
Humoral
- Neutralization of viruses (how vaccines work)
- Phagocytosis
- Antibody-dependent cell-mediated cytotoxicity
- Complement activation
Cell-mediated
- CD8 kill viral-infected cells via MHC-1
- CD4 Th1 activate phagocytes, promote B cell & CTL responses
How to diagnose a viral infection
- Virus cell culture
- Antigen detection (ie EIA, DFA)
- Molecular diagnosis (ie PCR)
- Serology (IgM, IgG)
- Electron microscopy
- Histology (eg CMV inclusion bodies)
Antivirals considerations
Consider the 9 stages of a viral infection upon where to attack the virus
- Recognize cell for which it has tropism
- Attachment
- Penetration
- Uncoating
- Transcription
- Protein synthesis (INF; ribaviron)
- Replication (nucleoside analogues)
- Assembly (protease inhibitors)
- Lysis & release (neuraminidase inhibitors)
Antivirals that act at the uncoating stage?
- Amantidine
- Rimantidine
Uncoating stage antivirals moa
- Bind to M2 protein of influenza A
- Most influenza A are now resistant to amantidine & Rimantidine
Amantidine Class
Uncoating stage antivirals
Rimantidine class
Uncoating stage antivirals
Uncoating stage antivirals side effects
Anticholinergic side effects
ADE AKA
Adverse Drug Event
Antivirals acting at the transcription and/or protein synthesis stage
- Ribaviron
- Interferon
Antivirals acting at transcription and/or protein synthesis stage MOA
Ribaviron: Blocks RNA polymerase
Antivirals acting at transcription and/or protein synthesis stage used for
Interferon rarely used but ribaviron still used for the treatment of HCV
Antivirals that are nucleoside analogues
5 listed
- (Val)acyclovir
- Famciclovir
- (Val)ganciclovir
- Foscarnet
- Cidofovir
(Val) prefix
oral form
(Val)Acyclovir MOA
Viral thymadine kinase phosphorylates acyclovir (1st time; host then does times 2&3) so can actively inhibit viral DNA synthesis HSV, VZV,
(Val)Acyclovir ADE
- Nephrotoxicity
- alteration or absent/deficient TK or altered viral DNA polymerase
Famciclovir MOA
prodrug of penciclovir
HSV
VZV
Famciclovir ADE
- alteration or absent/deficient TK or altered viral DNA polymerase
(Val)ganciclovir MOA
Phosphorylated by viral TK in HSV and viral phosphotransferase (encoded by UL97) by CMV
drug of choice for CMV
also active against HSV, VZV
(Val)ganciclovir ADE
- bone marrow suppression
- mutation of UL97 or viral DNA polymerase
Foscarnet MOA
does not require phosphorylation like ganciclovir-R
CMV
Foscarnet ADE
- Nephrotoxicity
- bone marrow suppression
- low K/Mg
- altered viral DNA polymerase
Cidofovir MOA
fully phosphorylated by host enzumes so independent of TK
acyclovir-R HSV
ganciclovir-R CMV
Cidofovir ADE
- bone marrow suppression
- renal tubular acidosis
Antiviral that act at the assembly stage MOA
Protease inhibitors
Antiviral that act at the assembly stage clinical use
Used for treatment of HIV & chronic HCV
Antivirals that act at the lysis & release stage
Neuraminidase inhibitors:
- Oseltamivir
- Zanamivir
Antivirals that act at the lysis & release stage MOA
Inhibit release of Influenza A&B
Antivirals that act at the lysis & release stage ADE
Zanamivir can cause bronchospasm
Zanamivir dose type
inhalation
Types of DNA viruses
Naked & Enveloped
Types of RNA viruses
3 listed
- single-stranded negative-sense (all enveloped)
- Double-stranded segmented (all naked)
- Single-stranded positive-sense (some naked and some enveloped)
DNA viruses rules
- All DNA viruses are double-stranded (Except Parvo Virus)
- Transcription occurs in the nucleus (except Poxviruses where replication occurs in the cytoplasm)
- All contain DNA polymerase (except Parvo, Papilloma, polyoma viruses)
Parvo virus type
Single-stranded naked DNA virus
Poxvirus replication occurs where
Occurs in the cytoplasm
Caveats of Parvo virus
- single-stranded DNA virus
- Don’t contain DNA polymerase
DNA viruses that do not contain DNA polymerase
- Parvo Virus
- Papilloma Virus
- Polyoma Virus
Naked DNA viruses
4 families
- Parvovirus B-19
- Adenovirus
- Papillomavirus HPV
- Polyoma Virus (JC, BK)
Parvovirus B-19 type
Single-stranded linear naked DNA virus
Parvovirus B-19 Dx
- PCR
- IgM
- IgG
Adenovirus type
DS linear Naked DNA Virus
Adenovirus Dx
NP DFA/PCR
Papillomavirus HPV virus type
DS circular Naked DNA
Papillomavirus HPV Dx
?
Polyoma virus type
DS circular Naked DNA virus
Polyomavirus Dx
PCR
JC virus type
polyoma virus
BK virus type
polyoma virus
Hepadnavirus type
Hepatitis B virus
DS circular enveloped DNA virus
Vaccine preventable
Poxviridae virus type
DS linear enveloped DNA virus
Examples of Poxviridae viruses
- Molluscum contagiosum
- Smallpox
Herpesviridae virus examples
- HSV 1
- HSV 2
- VZV
- EBV
- CMV
- HHV6
- HHV7
- HHV8
Herpesviridae virus types
DS linear enveloped DNA virus
Latent
Herpesviridae virus Dx
DFA
PCR
IgM > Cx
Herpesviridae virus Tx
Nucleoside inhibitors
HSV1 viruse type
Herpesviridae
DS linear enveloped DNA virus
HSV 2 virus type
Herpesviridae
DS linear enveloped DNA virus
VZV virus type
Herpesviridae
DS linear enveloped DNA virus
EBV virus type
- Herpesviridae
- DS linear enveloped DNA virus
CMV virus type
Herpesviridae
DS linear enveloped DNA virus
HHV6 virus type
Herpesviridae
DS linear enveloped DNA virus
HHV7 virus type
Herpesviridae
DS linear enveloped DNA virus
HHV8 virus type
- Herpesviridae
- DS linear enveloped DNA virus
Features of SS negative-sense RNA viruses
Require RNA-dependent RNA polymerase
All are enveloped
Categories of SS negative-sense RNA viruses
- Filoviridae
- Bunyaviridae
- Rhabdoviridae
- Orthomyxoviridae
- Paromyxovirdae
Filoviridae examples
Ebola
Bunyaviridae examples
Hanta virus
Rhabdoviridae examples
Rabies
Orthomyxoviridae examples
- Influenza A
- Influenza B
Paromyxoviridae examples
- Measles
- Mumps
- parainfluenzae
- RSV
- Human metapneumovirus
Paromyxoviridae Dx
Measles, Mumps
- Dx: IgM
parainfluenzae, RSV, Human metapneumovirus
- Dx: NP swab, BAL
Orthomyxoviridae Dx
NP swab
BAL for DFA or PCR
Orthomyxoviridae Tx
Neuraminidase inhibitors
Features of SS positive-sense RNA
Act as mRNA
Bind to ribosome for direct protein synthesis
Either naked or enveloped
Classes of enveloped SS positive-sense RNA viruses
- Togaviridae
- Flaviviridae
- Coronaviridae
- Retroviridae
Togaviridae examples
Rubella
Alphaviruses
Eastern equine enceph
Western equine enceph
Chikungunya
Flaviviridae examples
WNV
St. Louis encephalitis
Yellow fever
Dengue
Hep C Virus
Flaviviridae Dx
- Serology
- PCR
Coronaviridae examples
SARS
MERS-CoV
Retroviridae contain
RNA-dependent DNA polymerase
Retroviridae examples
HIV
HTLV-1
Retroviridae Dx
HIV
Dx: Ab
HTLV-1
Dx: ?
Retroviridae Tx
HIV
Tx: HAART
HTLV
Tx: ?