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