viruses Flashcards
what family does poliovirus belong to? genus?
- family: piconarividae (small)
- genus: enterovirus
what are the general characteristics of poliovirus?
- small (7-8.5 kb)
- naked
- ssRNA genome
- whole genome is translated into a single polyprotein that cleaves itself into viral proteins
what is the host/reservoir /vector for poliovirus?
mainly humans
what part of the body does is affected poliovirus and what is the receptor it binds to?
- intestinal mucosa
- receptor is CD155 (present on almost all cells of the body - muscle and mucosal cells)
- CD155 is also found in central nervous system which is why polio virus can cause paralytic polio (this is an error of the virus and a dead end for spread)
where does poliovirus replicate?
-mainly in the gastrointestinal tract
what are the modes of entry for poliovirus?
- enters body through contaminated food and water sources (fecal-oral route)
- when the virus binds to the host receptors, one of the capsid proteins is removed to allow infection of viral genome into the host cell
- viral progeny is released by lysis of the host cell
how does poliovirus avid host defences?
- fast paced replication that overwhelms host system so virus has time to infect cells and replicate
- two viral proteases interfere with host cell natural function
- partial resistance to type I interferon: two proteases 3Cpro and 2Apro cleave MDS-5, RIG-1, MAVS that interefere with interferon synthesis and expression of proteins that are involved in the antiviral state (may also cleave NK-kappa,beta which surprises the expression of cytokines and interferons
- it replicates in the cytoplasm and uses membranes of host cells secretory pathway to generate replication complex and replication organelles for viral RNA synthesis so it avoids sureveillance of intracellular dsRNA detection mechanism (can manipulate COPII secretory vesicles)
what are the two viral proteases that poliovirus uses to interfere with hosts cell functions?
viral proteases 3C:
-travels to nucleus and interferes with transcription of host genes
-interferes with activity of host RNA pol. as well as induces the cleavage of TATA box
-the cleavage of transcription and translation initiation factors the control cell survival and death pathways result in the induction of apoptosis on host cell
viral protease 2A: c
-cleaves several of the translation initiation factors (eIF-4G) that are necessary for cap-dependant translation of host mRNA
-this favours viral translation because the genome doesn’t have a 5’cap but an IRES instead and doesn’t requires the participation of protein normally associated with initiation complex in the translation on normal 5’ capped host mRNA
what do all positive sense RNA viruses do to generate new compartments?
- they confiscate intracellular membranes of host cells in order to generate new compartment for amplification of their genome
- this provides mechanism to avoid detection of dsRNA molecules during transcription and replication of viruses
what is the mode of transmission for poliovirus?
- virus transmitted fecal oral route
- can remain infectious in environment for a while
disease and symptoms of poliovirus?
- flu-like
- fatigue, sore throat, vomiting, loss of appetite
what are the complications that can come from poliovirus?
- may enter CNS and attach to receptor in motor neurone causing paralytic polio (1/200)
- damages nerve cells and causes distruction of motor neurons
- cell lysis destroys nerve function
when does poliomyelitis occur from poliovirus?
- when the virus spread from intestine to muscle nerve cells (happens because motor neurons synapse same receptor C155 found in intestinal epithelial cells
- paralysis from motor neuron damage is often permanent
treatment and prevention for poliovirus?
- disease is usually self limiting which means the immune system eventually develops full immunity to virus
- vaccines are available in oral polio vaccine from OPV which is an attenuated virus
- other vaccine is Inactivated polio vaccine IPV that must be injected
what issues can occur with the OPV vaccine for polio?
- vaccine associated poliomyelitis paralysis when there’s a mutation that causes reversion of attenuated strain into virulent strain
- called VAPP (vaccine-associated poliomyelitis)
- rare event
what are the special features of poliovirus?
- virus genome double as mRNA so the first event upon infection is viral protein synthesis
- virus genome does not have cap , it has VPg proteins at 5’end, ribosomes do translation of viral genome using internal ribosomal entry site (IRES)
what family does dengue virus belong to?
-flavividae (after yellow fever)
what are the general features of dengue?
+ssRNA
- enveloped
- protein dominated envelope fives virion a gold ball appearance
- genome encodes for one single ORF which is translated into a poly protein (like picornaviridae)
- genome has 5’cap and is translated at rough ER
what are the hosts/reservoir/vector for dengue?
- primary host is humans, other mammals like monkeys can be infected too and many act as reservoirs (especially in West Africa and south east Africa)
- vector: female Aedes aegypti (yellow fever mosquito ) and Aedes albopictus (asian tiger mosquito), could also be other biting insects or blood transfer from needle
- no direct person-person transmission
what part of the body is affected by dengue?
- virion enters host (via arthropod vector) by binding to host cell receptor and being endocytosed
- viral envelope glycoprotein E is primary cellular anti-receptor
- exact receptor site and interaction unknown
- first cells to be infected are monocytes, macrophages and dendritic cells (likely responsible for dissemination of virus after initial infection)
- some studies say 1st cell infected by virus are skin dendritic cells (langerhan cells) that migrate to lymph nodes and infection spreads to monocytes and macrophages
what are the modes of entry and exit from the host cell?
- receptor is unknown but entry is via receptor mediated endocytosis
- translation of genome take place in ER
- exits by exocytosis (viral progeny bud from host membrane)
how does dengue virus avoid host defences?
-virus infects cells of innate immune system, enabling them from doing their job
-NS1: necessary for RNA replication, antagonism of host complement response. NS1 proteins bind to complement component C4 and actively cleave C4 to C4b limiting activation of complement proteins, acts as a suppressor of classical and lectin pathways of complement
NS2A: cofactor activity, disrupts host cell interferon regulation
NS4B: disrupts host cell interferon regulation, regulates viral envelope assembly
how does DENV evade innate immune response?
- blocks type I interferon, can inhibit production and signalling of it
- NS2A and NS3 inhibit IFN-I production by degrading cellular signalling molecules
- NS2A, NS4A, NS4B, and NS5 inhibit IFN-I signalling by blocking phosphorylation of STAT1 and STAT2 molecules
- NS5 also mediates degradation of STAT2 using proteasome machinery
what is the mode of transmission for dengue?
-mosquito vector but also contaminated needles or tools (direct blood transmission)
what are is the disease and its symptoms that is caused by dengue?
- dengue fever (acute febrile illness with sudden onset of fever followed by development of generalized symptoms and sometimes a macular skin rash)
- known as breakbone fever: can cause severe muscle, joint and bone pains
- pain behind eyes may be present
- fever can be biphasic (two waves)
- most patients recover after a few days
what is dengue hemorrhagic fever?
-acute onset of fever followed by symptoms resulting in thrombocytopenia (increased vascular permeability and hemorrhagic manifestations
what is dengue shock syndrome?
- rare
- sever hypertension develops and urgent medical care is required to correct to hypovolaemia
- without care, 20% of cases are fatal, with care its 1%
treatment and prevention for dengue?
- no antiviral drugs
- self-limiting disease (individuals only become immune to serotype that causes infection through)
- to prevent, limit where mosquitoes can breed
- could maybe use drug against NS1 activity
- developing a vaccine is difficult
- Dengvaxia is a newly approved attenuated vaccine that targets all 4 serotypes (possible risks of severe dengue when individual is immunologically naive)
