Week 24 - virus structure, replication cycle and prions Flashcards
Viruses
The most abundant biological entities on Earth -> around 10 nonillion (10^31) viruses on our planet
Different viruses infect all organisms
->Some contribute to microbiota
->Some infected cells can carry viral genomes lifelong (e.g. herpetic viruses) -> once infected with those viruses, it is for life
Foundation of viruses
Acellular Infectious particles (10-400 nm)
->Carry genetic material (either DNA or RNA – never both)
-Do not grow or undergo division outside a cell
-Obligate intracellular parasites – can only replicate in host cells !!! They lack necessary cell metabolism to produce and assembly viral progenies (make copies of themselves)
Viruses are NOT bacteria Antimicrobial stewardship principles:
-Antibiotics are not effective against viruses
->Specific virus infections should be treated with antiviral agents
Virus general characteristics
Viruses can only be seen through electron microscopy (not by a light microscope)
Virus composition
Virion (mature virus outside a cell) is composed of:
-Nucleic acid - DNA or RNA complexed with matrix proteins or enzymes
-Capsid - protein coat to protect the genome
-Envelope – External occasional lipid bilayer membrane on some viruses, containing peripheral glycoproteins (e.g., spikes) projecting outward
Presence/absence envelope
Naked virus -> Envelope is not present in naked viruses
Enveloped virus -> Envelope is present in enveloped viruses - more susceptible to disinfectants
Viral envelope
->External layer (in enveloped viruses only)
-A lipid bilayer derived from host cell membrane
-Acquired by budding when viruses leaves the infected cell
-Contains viral glycoproteins (e.g., spikes)
Viral envelope glycoproteins
Viral glycoproteins embedded in the envelope lipid bilayer:
-Synthesised through the secretory pathway
-Proteins destined to the plasma membrane
Facilitate attachment and fusion to cell receptors for entry -determing tropism -> specific extracellular receptors
Often form spike-like structures –> protruding outward
Viral capsid
Protein shell that encases and protects the viral genome
->Composed of repeating protein subunits called capsomers
->During infection, capsomers self-assemble around the viral genome
Capsid arrangements - shapes
Helical - hollow, cylindrical
Polyhedral - spherical
Complex
Nucleic acid
Viral genomes:
-Contain the genetic information required for viral replication
-Can be DNA or RNA - double-stranded (ds) or single-stranded (ss), linear or circular
-Low size genomes contains few genes (4 to 100) encoding proteins needed for: viral structure, genome replication,
immune evasion, hijacking cellular metabolism
-Replication occurs within the host cell, often using the host’s machinery
-Some viruses can integrate their genome into the host’s DNA
Viral tropism
Refer to the specific host cells that a virus can infect Determined by the presence of specific:
-Host cell receptors (to mediate viral entry)
-Required cell enzymes (to complete the viral cycle)
Bacteriophages or phages -> viruses that infect only bacteria
->RBP receptors only in bacteria
Viral replication cycle (generic)
Series of events that a virus needs to undergo to form viral progenies inside a host’s cell during infection
Steps are virus-specific -> some viruses have additional steps
1)Attachment
2)Penetration
3)Uncoating
4)Release
5)Protein synthesis
6)Biosynthesis
1)Viral attachment
Virus adheres to cell surface (random collisions & electrostatics) -> no specificity required
->Attachment to specific receptors on cell surface by envelope glycoprotein or
external capsid protein (naked viruses)
2)Virus penetration
After attachment, viruses penetrate the cell in 2 ways:
In Enveloped viruses:
-Fusion between viral envelope and host cell membrane -> thus, releasing the capsid intracellularly
Naked viruses (e.g. Adenovirus, Adv):
->By endocytosis, which engulfs the virus into cellular vesicles
-Receptor binding triggers the process of endocytosis
-Cell membrane is pinched off
-The virus is engulfed
-A vesicle is formed (Endocytosis)
3)Uncoating
Virion uncoating - genome release
Viral uncoating or transcapsidation
->Process of capsid disassembly to release the viral genome into the cytoplasm
->Viral genome migrates into the nucleus, to start transcription of viral genes and genome replication
4)Virus genome replication and protein synthesis
Viruses hijack the host cell synthesis machinery and turn it into a virus factory to:
-Replicate their genome
-Synthesise viral proteins
-Transcription of viral genes into mRNA in the nucleus
-Translation of mRNA into proteins by cell ribosomes in the cytoplasm
-Depends on the genome types and regulated by viral and cellular enzymes
5)Protein maturation and virion assembly
Protein maturation and virion assembly
Protein maturation:
-In many viruses, the whole viral genome is transcribed and translated into large precursor polyproteins, which are unfunctional and immature
-This precursor is processed by viral & cell proteases to form individual, functional and mature viral proteins
Virion assembly:
-Capsomers assemble enclosing the replicated viral genome and some viral enzymes to form a capsid
-A single infected cell produces 104 / 106 new virions
6)Release of new virions
Viral release -> mature viral progenies exit the infected cell to infect others
Mechanisms differ in naked and enveloped viruses:
Budding / exocytosis ->Enveloped viruses:
-Assembled new capsid particles bind the membrane
-The membrane pinches off and viruses bud off carrying away the envelope with their spikes
-Infected cells does not die
Lysis –> Naked viruses
-Viruses induce cell death
-Cell bursts and virions are released
Prions
Proteinaceous infectious particles – misfolded proteins
DO NOT contain nucleic acids
Cause transmissible spongiform encephalophaties -> cause fatal neurodegenerative diseases
Transmissible:
-By ingestions of contaminated tissue (contaminated meat),
-Contaminated surgical instruments
->Genetic inheritance – mutations in the PRNP gene
Spongiform encephalopathies
Rapid and progressive neurodegenerative disorders
->Characteristic microscopic holes in the brain’s cortex, with a spongy appearance
->Cause progressive impairment of brain function
Symptoms:
-Cognitive decline
-Involuntary movements
-Lack of coordination
-Always fatal
-No cure
Prions - characteristics
Extremely resistant to standard sterilization techniques:
->Such as standard autoclave programs of 121 degrees C
for 15 minutes (more than bacterial endospores)
->Prion inactivation requires autoclave cycle at
134°C for 18 minutes or more
