Viruses Flashcards
what is a virion?
a delivery system that surrounds a payload
what is the payload of the virion constitute?
structural components used by the virus to survive in the environment (viral genome + enzymes for initial viral replication)
what is a capsid?
a single or double layer protein shell that surrounds the nucleic acid of a virus
what is a nucleocapsid?
when the capsid surrounds the nucleic acid
what are the subunits that form the capsid called?
capsomers
how are the viral capsid proteins arranged?
icosahedral:-
- 20 triangular faces, 12 vertices
- spherical
- nucleic acid inside the spherical core
Helical:-
- proteins bound in a regular periodic fashion along nucleic acid
what is the difference between enveloped and non-enveloped viruses?
enveloped viruses possess an envelope that surrounds the nucleocapsid whereas the non-enveloped don’t
what does the viral envelope contain?
- virus specific proteins (matrix proteins)
- lipids
- carbohydrates
where is the matrix protein located?
it lines the inner surface of the viral envelope and is in contact with the nucleocapsid
what is the function of matrix proteins?
- stabilize the interaction between viral glycoproteins and the lipid envelope
- direct the viral genome to intracellular sites of assembly
- help in virus budding
briefly, what are the general steps in virus replication?
- attachment & penetration
- macromolecular synthesis
- assembly of progeny virions and release from host cells
- dealing with defective viruses
define adsorption
attachment of the virus to the host cell surface as a result of random collision between the virions and the target cell
(first step of viral infection of a susceptible cell)
how are viruses able to attach to cell surfaces?
viruses have attachment proteins to facilitate adsorption, for example hemaglutinin in influenza
describe the mode of attachment of enveloped and nonenveloped viruses
Enveloped viruses: have more than one attachment protein on their surface
Nonenveloped viruses: they have surface exposed regions of capsid proteins to mediate virus attachment
how are some viruses able to attack different cell types?
some viruses use multiple receptors as points of attachment which allows them to invade various cell types
what happens after adsorption?
payloaad is translocated across the plasma membrane of the host cell
how do enveloped and non-enveloped viruses gain entry to the inside of the cell?
-Enveloped viruses gain entry directly by fusing their envelop with the plasma membrane
-Non enveloped viruses: virus is taken by endocytosis and fuses with endosomal membrane inside the cell
continue the blanks
- non enveloped viruses bind at receptors that aggregate at the ________ & then endocytosed within clathrin-coated vesicles before delivery to endosomes
clathrin-coated pits
what is uncoating?
process in which the capsid is removed to make the viral genome accessible to cellular transcription and translation mahinery
TRUE OR FALSE
for many viruses, penetration and uncoating occur together
TRUE
How are capsids removed for nonenveloped viruses during replication?
by host cell enzymes
how are reoviruses capsids removed?
reoviruses have proteases in late endosomes, and lysosomes that remove the outer capsid proteins producing a subvirion particle
what is the function of a subvirion particle?
it penetrates endosomal membranes leading to activation of virus transcription in the cytoplasm
what is macromolecular synthesis in viral replication?
translation of viral mRNA into virus specific proteins
what enzyme is used to produce viral RNA?
Virus-encoded RNA-dependent RNA polymerase
how is positive sense RNA produced during macromolecular synthesis?
virus encoded RNA dependent RNA polymerase synthesizes a negative sense RNA that serves as a template for the synthesis of positive sense RNA that is then packaged into progeny virion
TRUE OR FALSE
viral RNA acts as mRNA, translated by cellular ribosomes to produce viral proteins
TRUUUE
how is mRNA translated in poliovirus?
mRNA is translated to a single large polyprotein that is cleaved by virus encoded proteases to release individual viral proteins
How is negative sense RNA synthesized in macromolecular synthesis of viral replication?
During replication of the viral genome, RdRp synthesizes a positive-sense antigenome that it uses as a template to create genomic negative-sense RNA
why must double stranded RNA viruses copy their RNA strands to single positive sense RNA?
because the double stranded character of RNA cannot function directly as mRNA, thus it must be copied to single positive sense RNA for it to act as mRNA
which enzyme is used to generate a negative strand of the double stranded RNA to synthesize a single stranded positive sense RNA?
- virus encoded RNA dependent RNA polymerase
explain the process of RNA replication through DNA intermediates
positive sense RNA serves as a template for the enzyme (RNA dependent DNA polymerase), whereby DNA is then integrated into host chromosomal DNA and transcription is carried by host cell DNA dependent RNA polymerase
what virus is an example of viral replication that occurs through DNA intermediates?
Retroviruses (HIV)
How do DNA viruses, like herpesvirus, make mRNA?
by using strategies similar to those of the host cell’s, they are tightly regulated and result in synthesis of early and late mRNA transcripts
what is the difference between early and late mRNA transcripts?
early transcripts: encode regulatory proteins and proteins required for DNA replication
Late transcripts: encode structural proteins of the virion
why is it that poxvirus is unable to use host RNA polymerases during replication?
because the initial steps of transcription and translation occur in the host cell cytoplasm, and RNA polymerases are located in the nucleus
however, poxvirus carry its own DNA-dependent RNA polymerase to initiate transcription
what happens after the process of macromolecular synthesis?
intact virions are assembeled and released from host cells
nucleocapsid formation (viable virions)
what events lead to viral cell death/disruption
- inhibition of host macromolecular synthesis
- disorganization of host cell cytoskeleton
- alteration of host cell membrane structure
how are enveloped and non-enveloped viruses released?
non enveloped: upon cell death
enveloped: from infected cell by budding
how do viruses kill cells?
by apoptosis characterized by cell shrinkage, membrane blebbing, condensation of nucleur chromatin, and cleavage of cell DNA
What is a defective virus?
A virus particle that contains insufficient nucleic acid to provide for production of all essential viral components
what is an example of a defective virus?
Hepatitis delta, for hepatitis delta to manifest, one must also be infected by Hepatitis B, which allows the replication of hepatitis delta
how are defective viruses diagnosed?
- by antigen search
- culture in the presence of a helper virus
define a helper virus
virus that allows an otherwise-deficient coinfecting virus to replicate
what are the characteristics of herpes virus?
- double stranded DNA genome
- icosahedral nucleocapsid
- enveloped
- life-long latent infections
what are herpesvirus subfamilies?
- alpha (HSV1/HSV2/VZV)
- beta (cytomegalovirus/HSV-6/HSV-7)
- gamma (Epstein barr/HSC-8)
How are HSV-1 & HSV-2 transmitted?
HSV1 → oral-oral / oral-genital
HSV2 → oral-oral / oral-genital / genital-genital
How is VZV transmitted?
Respiratory route via aerosols/vesicular fluid
why is it that asymptomatic HSV infected patients can still transmit the infection?
because shedding from epithelial surfaces can occur even if lesions aren’t noticeable
TRUE OR FALSE
HSV is almost always asymptomatic, VZV is almost always symptomatic
TRUE
what organs does herpes virus infect?
mainly mucous membranes (genitals,mouth, respiratory tract,anus,eyes)
what is the first line of defense against herpes?
skin
how come herpes affects mucos membrane but not skin?
the thick keratin layer of the superficial epidermis prevents access of HSV to its receptors, and because mucous membranes present a more formidable barrier that is readily affected
how does herpes virus infect cells?
- attaches to susceptible cell
- glycoproteins projecting from viral envelope inteact with surface receptors
- glycoproteins interact with heparan sultate chain on the proteoglycan and bind to it
- virus will be close to molecules that facilitate its entry
- binding triggers fusion of viral envelope with either cell membrane or plasma membrane
- viral nucleocapsid is released into the cytoplasm
- viral genome released into nucleus
- replication occurs inside the cell in temporal fashion (proteins→genome→progeny virions)
what is a herpesvirus latent infection?
viral genome circularizes in the nucleus as an episome with minimal gene transcription
when do you refer to an infection as productive infection?
when virus replication occurs, immediate early genes are transcribed with transcription factors in the virion tegument
what is a virion tegument?
space between nucleocapsid surface and envelope
what are the proteins encoded by immediate early genes?
- early genes: required to replicate viral DNA
- Late genes: encode proteins that assemble and comprise progeny virions + glycoproteins inserted into cell membrane
what immune responses occur in herpes virus?
neutrophils
NK cells
Cytokines
Interferons
t lymphocytes
why is it that the immune system is unable to get rid of herpesvirus 1 & 2?
because cells of latent infections do not stimulate the immune system, thus it does not attack it
who is considered a risk patient for HSV?
neonatal HSV, which could be lethal due to greater innate susceptibility and immunological immaturity
what tissue does HSV infect?
epithelial, causing vesicular lesions that rupture to a shallow gray/white ulcers on en erythmatous base
why are HSV infected epithelial tissues able to fully regenerate?
because viral replication and spread are contained by innate and cell mediated response
what causes symptoms of itching, tingling, burning, and pain in HSV infected patients?
because of the damage and inflammation to nerves during acute phase of infection
what triggers reactivation of HSV?
- immune impairment
- emotional stress
- menstruation
- sunburn
how is herpes treated?
nucleoside analog drugs such as acyclover
what is the mechanism of action of a nucleoside analogue (e.g. acyclover)?
it is phosphorylated by herpes enzymes and incorporated into viral DNA as a chain terminating nucleotide since it is a guanosine analog
what is a prodrug?
drug substance that is inactive in the intended pharmacological actions and it must to be converted into the pharmacologically active agent by metabolic or physico-chemical transformation.
what are prodrugs of acyclover?
valacyclover
lialacyclover
what is one key pharmacological feature of prodrugs?
they have improved oral bioavailability
TRUE OR FALSE
long term treatment with acyclover prevents hsv recurrences and flare ups
TRUE
what genes are required for retroviral replication?
- gag (core proteins)
- pol (RNA dependent RNA polymerase/integrase)
- env (gp120/gp41)
- pro (proteases)
what is the function of proteases in retroviruses?
cleave gag and pol to their active forms
what are the means of transmission of HIV?
- sexual intercourse
- vertical transmission (birth)
- IV drugs (through needles)
who is a risk patient for HIV?
Hemophilia, because they receive blood donations from thousands of donors and it’s from factors VIII & IX
what roles do genes have in HIV infection?
presence of CCR5 receptor is important for HIV infection, if it is defected, infection with HIV will progress very slowly to aids
why is it that the 2 RNA molecules resemble eukaryotic mRNA in retroviruses?
because they contain a cap structure at the 5’ end and a polysequence at the 3’ end
what is the main target of HIV?
- Helper t-lymphocytes (CD4)
- monocytes
what are the steps of HIV infection?
- binding
- fusion
- DNA synthesis
- integration
- latency & transmission
- progeny virion synthesis
how does HIV bind to CD4?
HIV binds to CD4 via gp120 which reacts with CCR5 or CCR4 making attachment easier on the cell surface.
what happens after gp120 binding to CCR5/CCR4?
a conformational change, bringing hydrophobic domain of the protein in apposition with cell membrane.
which enzyme facilitates the release of the viral core into the cytoplasm?
reverse transcriptase
what does integrase do in viral replication?
catalyzesthe transport of DNA to the nucleus by joining LTR and host cell DNA
what is a provirus?
viral genetic material in integrated state, which is analagous to cellular gene (passed to daughter cells at division)
what does LTR do?
directs RNA synthetic machinery
explain transactivation
when the expression of HIV macromolecules is subject to regulation by viral gene products that operate at soluble elements
what are the viral genes that contain transactivating factors?
Tat
Rev
what is the function of transactivating factors?
increase the expression of viral RNA proteins
what does tat do?
accelerate transcription of viral RNA by host RNA
what does rev do?
enhances transport of viral RNA from nucleus to cytoplasm
Bonus fact
when infected with a provirus, infectious process may be halted, and then reinitiated explosively due to high level of transactivation
read that again
what are the genes that facilitate evasion of virus specific immune responses
nef: downregulated cell surface expression of MHC-1
vif: facilitate destruction of ABOBEC 3G
vpu: downregulated tethrin
how does HIV persist in the body despite immune response?
because virus gene products are invisible to immune cells, they change their antigenic specificity and replicate in lymphoid follicles
which HIV gene products direct immune response?
gag +pol → show stability from one isolate to another
env: mutations that lead to variation in its products (gp120/gp140)
true or false
some antibodies can neutralize viruses
true
what are the properties of the viral envelope?
- extensive polysaccharide coating, limits immunogenecity
- hypervariable regions, permit virus to present new antigenic variation to host
which gene gives the virus the ability to change its antigens?
gp120
how does gp120 provide antigenic variation?
by hiding conserved sequences, thus protecting them from the neutralizing antibodies by carbohydrates and hypervariable region
what is the function of RNA transcriptase?
uses RNA to as a template similar to that of the human’s to produce DNA. (Reverse transcription)
such viruses are capable of causing cancer
what is the mechanism of action of non-nucleoside reverse transcriptase inhibitors?
prevent HIV from replicating by blocking the reverse transcriptase enzyme.
what is acute HIV infection
Acute HIV infection is the earliest stage of HIV infection, and it generally develops within 2 to 4 weeks after infection with HIV
what is the immune response against acute HIV
cytokines - chemokines
what happens after a few week after HIV infection?
- virus specific cytotoxic t cells appear in peripheral blood and lymphoid tissue
- neutralizing antibodies are detected in plasma
what is the primary cell target of HIV?
99% CD4
1% monocytes & resting CD4 Tcells
what leads to progressive immunodeficiency (aids) in HIV?
the loss of CD4 & t cell population. with a count of 50cells/ mm3
normal count is = 1000 cells/mm3
HIV count is = 200 cells/mm3
what does a high virus load in plasma indicate (105 copies)
HIV disease progression to AIDS within a few years
define lymphopenia
decreased number of t cells
how does HIV cause immunodeficiency?
by causing t cells to malfunction, leaving the body unable to produce antigens, therefore the patient becomes immunodeficient
what is the main cause of death in AIDS patients?
pneumonia jiroveci and mycobacterium tuberculosis
how is HIV/AIDS diagnosed?
cell culture
PCR assay
serologic test
why is it that during the diagnostic testing of HIV, absence of antibodies does not exclude HIV infection?
because some patients lose their antibody detection due to the long time they have been infected with the virus
what is the initial test for HIV?
ELISA (twice) because it has a possibility of false-positive
what classes of drugs are used for HIV?
nucleoside reverse transcriptase inhibitors
didoxynucleotides
nonnucleoside reverse transcriptase inhibitors
protease inhibitors
what is the mechanism of action of NRTI
When RT is creating new DNA, it inserts a molecule of zidovudine rather than a nucleoside this terminates DNA chain and no more can be appended to it
what is the mechanism of action of NNRTIs
NNRTIs attach to the reverse transcriptase and affect the activity of the enzyme by restricting its mobility and making it unable to function
what is the mechanism of action of protease inhibitors?
HIV protease inhibitors binds to enzyme active site, thus HIV virus unable to process proteins
what is the mechanism of action of neuraminidase inhibitors?
inhibition of the activity of the viral neuraminidase, preventing the release of virions
what are the 3 enteroviruses?
polioviruses
echoviruses
coxsackieviruses
where is poliovirus found?
feces 💩
what what causes poliomyelitis?
polioviruses found in feces, due to contaminated water or through fecal-oral route
where do polioviruses replicate?
oropharyngeal and intestinal mucosa
do polioviruses enter the blood stream?
yes, causing viremia within 7 days of infection with a poliovirus
what is a rare complication of polioviruses?
1% invade CNS causing paralysis 11-13 days after infection
why certain sites don’t allow replication of poliovirus even though all cells have CD155?
due to tropism, influenced by host immune response, and cell is protected by interferons that put tissue in antiviral state
what are the properties of the coronavirus?
- enveloped
- positive sense RNA virus
- responsible for 30% of common colds
- undergoes rapid genetic change
what is SARS?
Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus.
what is SARS COV derived from?
Bats
what is the function of RNA dependent RNA polymerase in coronaviruses?
can jump between RNA templates resulting in RNA-RNA recombination
what is the function of RNA exonuclease in coronaviruses?
mediate RNA proofreading and regulate replication fidelity
how are coronaviruses able to adapt to various new hosts?
coronaviruses have RNA dependent RNA polymerase which can jump betweenn RNA template resulting in RNA-RNA recombination,
and they have RNA exonuclease which mediates RNA proofreading and regulate replication fidelity
what is antigenic drift and antigenic shift?
antigenic drift: accumulating changes in hemagglutinin and neuraminidase
antigenic shift: novel hemagglutinin and neuraminidase by exchange of genes with another virus
define reassortment
process of exchange of genes with another virus
what is the structure of influenza virus
RNA segments encapsidated by viral nucleoprotein + 3 virus encoded polymerase proteins (PA/PB1/PB2) and M proteins, surrounded by host derived lipid membrane
how many proteins does the RNA of influenza encode, and in how many segments?
8 segments, 12 proteins
what is the peak season for influenza encounter?
october-april
december-march
how does influenza gain entry to the body?
via aerosols and direct contact, through the upper and lower respiratory tract
what cells are the first to be infected with influenza?
nonciliated epithelial cells
what is the incubation time of influenza?
2-3 days
what receptor is the preferred target for influenza?
terminal siacilic acid with 2-6 linkage to galactose
what is influenza infection manifestation dependent on?
neutralizing antibodies and immune interferons
what drugs can be used to treat influenza?
neuraminidase inhibitors, prevent the removal of cell surface sialic acid, thus inhibiting spread of virus to uninfected cells
what is the mechanism of action of amantadine?
inhibit uncoating and genome release into the cytoplasm, directing release back to the nucleus. this allows the formation of viral nucleoproteins and budding of new particles from cytoplasm, and then neuraminidase removes sialic acid receptors from the virus particle and cell surface leaving them unable to adhere to cell surface and each other
what are the complications of influenza?
primary viral pneumonia
bacterial pneumonia
otitis media
in children: reye syndrome (brain swelling/fatty degeneration)
how is influenza diagnosed?
mainly based on symptoms, or nose/throat swab for sputum
culture with chicken eggs
RT-PCR immunoassay
hemagglutinin inhibition test for previous infections
what is the most effective treatment of influenza?
prophylactic treatment via vaccines
what types of vaccines are there for influenza?
inactivated: formaldehyde-treated preparation, given intramuscularly, efficacy 60-90%, doesnt cause symptoms
live,attenuated, cold adapted: nasal spray, local mucosal response, longer lasting immunity, reactive against variants
why is it important that patients of coronary disease get vaccinated for influenza?
to lessen the chance of myocardial infarction complication
