viral Flashcards
basic virus structure
•DNA or RNA forms the core, which is surrounded by a
protein coat.
•Protein coat or capsid comprises protein units or
capsomeres
•Together the nucleic acid core and capsid form the
nucleocapsid
•In some viruses, the nucleocapsid is surrounded by an
- *envelope, a lipid bilayer of host cell origin**.
- envelope is studded with virus-encoded glycoproteins.
‘spikes’ in the viral envelope
attach virus to cell surface
mediate virus entry into cells
targets for antibodies
has carbohydrate side chain & transmembrane anchor
viral life cycle
extracellular phase in which virus particle
(“virion”) is metabolically inert and
intracellular phase in which virus genome
expression occurs; this, together with
involvement of host proteins (animal, plant or bacteria)
and other host functions, achieves production of
new progeny virions.
Viruses are obligate intracellular pathogens
enveloped vs nonenveloped
Non-enveloped “naked” viruses tend to survive well
(& may be bile resistant)
– e.g_. picorna (polio; hepatitis A) norovirus_
• Enveloped viruses often survive transiently outside
host. Spread by close or intimate contact
– e.g_. Influenza, HIV, Hepatitis B virus_
virus classification criteria
- Type of nucleic acid (DNA or RNA).
- • Symmetry of nucleocapsid
- • Lipid envelope (presence or absence).
- • Number of strands of nucleic acid (ss/ds) & their physical construction (e.g. segmented)
- • Polarity of viral genome (e.g. + or - strand RNA).
DNA viruses
enveloped:
poxvirus
baculovirus
herpesvirus
naked:
adenovirus
viral replication steps
- Attachment - to susceptible target cells
- Penetration - to cell interior (traverse membrane)
- Uncoating - primes for transcription
-
Transcription - production of viral RNA
* *5. Translation** - viral proteins produced - Replication - DNA or RNA, driven by viral proteins
- Assembly - new virions formed
- Release - & dissemination or transmission
key point: many critical functions and activities
are provided by the infected hos cell
how DNA virus replicates its genome
DNA viruses with large genomes e.g. poxviruses, herpesviruses encode 100 or more genes, including many of the enzymes required for genomic
replication (e.g. DNA polymerase) and are
more “autonomous”
DNA Viruses with small genomes e.g. papillomaviruses
encode only a few genes and use the host cell DNA polymerase etc
how RNA viruses replicate
Most RNA viruses encode their own
RNA-dependent RNA polymerase,
which uses complementary RNA as template
- *Retroviruses (& DNA Hepadnaviruses) ** encode Reverse Transcriptase - RNA-dependent DNA polymerase =>
- make dsDNA from RNA, for new genome synthesis
RNA dependent polymerases lack proofreading ability,
→ RNA viruses mutate quickly (& often replicate faster)
PLUS-STRAND RNA
Positive-stranded RNA is:
equivalent to mRNA and can often be immediately translated into proteins once the viral genome gains entry into the cytoplasm.
Therefore, protein synthesis is the first step, and
_one of the proteins synthesized is the viral
polymerase._The _polymerase then synthesizes
a *negative-strand copy of the +veRNA*, which is
then copied back into +veRNA messages._
Translation of these messages produces
structural proteins that are used to package
progeny +veRNA into virions.
MINUS-STRAND RNA
Negative-stranded RNA:
must first be converted into +veRNA (mRNA) by the RNA-dependent RNA polymerase (RDRP) incorporated in the virion.
The mRNA can then be translated into proteins.
Replicative enzymes (RDRP) synthesize a negative-strand copy of the +veRNA.
Structural proteins translated from the mRNA are
then used to package progeny -veRNA and RDRP into virions.
These types of viruses must package a polymerase into the viral capsid, because cells lack enzymes that will make a +veRNA copy of the viral -veRNA strand.
outcome after viral infection of cell
- *• Clearance** following acute phase of cell death
e. g. influenza, viral gastroenteritis, poliovirus, measles
• Persistent infection with continued production of infectious virus and immune evasion
e.g. hepatitis B, HIV
• Latent infection with virus persistence after initial clearance, and asymptomatic or symptomatic reactivation
e.g. Herpes viruses – herpes simplex, varicella zoster
latent virus infections
Viral DNA persists but does not replicate to
produce new infectious virus
• May never cause signs of disease.
• May activate on one or more occasions, and be
asymptomatic or cause disease.
• Some latent infections may lead to malignant
disease.
exposure
potential physical contact with virus
tropism
which cells/tissues (or host) are susceptible?
virulence
capacity to cause disease
VIral pathogenesis mechanisms
Cell death:
- Lytic infection, apoptosis,
- Immune mediated e.g. AIDS is attributable to the progressive loss of helper T cells
Interference with cellular function
– hepatitis, myocarditis, neuralgia
Body’s response to cell damage
– INCREASED mucous production in respiratory tract infections
Cell transformation and oncogenesis
Local effects of the immune response
– swelling, congestion, arthropathy, rashes
Systemic effects of the immune response
– fever
Immunosuppression
– Cytomegalovirus
– Measles
Triggering autoimmune response
– post-infectious encephalomyelitis
Defence:
Innate mechanisms
macrophages, neutrophils, NK, complement, interferon
defence: antibodies do what?
neutralise further spread
Viral mechanisms of Immune Evasion
Interference with cytokine network
mimic cytokine receptors - poxviruses
mimic inhibitory cytokines - EBV
inhibit interferon - adenovaccinia, influenza
suppress m-derived cytokines- measles
immune escape - antigen variation
mutation of epitopes RNA viruses > DNA viruses
antigenic “shift”/reassortment : influenza virus
ECLIPSE PHASE
Period from virus entry until new infectious virions released
INCUBATION PERIOD
Interval between exposure and appearance of rash/sign
PRODROME
Non-specific symptoms appearing before more specific features (usually rash)
