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Flashcards in Viruses and their treatment Deck (119):

what is the latent and eclipse periods of viral replication due to

when virus broken down into its particles and then amplication before genome assembled for release and spread


6 steps of viral replication

1. assembly 2. penetration 3. uncoating 4. amplification - genome replication, RNA synthesis and protein synthesis 5. assembly 6. release


how do viruses attach to cells

viral attachment protein binds specifically to a receptor (protein or carbohydrate) on the plasma membrane


what is the receptor for rhinoviruses

protein - ICAM-1


what is the receptor for influenza viruses

carbohydrate - sialic acid


attachment of HIV virus

2 receptors - initial and then closer attachment - initial attachment via gp120 to CD4 protein on T cells --> conformational change in the glycoprotein - exposing the hydrophobic portion of GP41 protein and recruits chemokine receptors - binding of chemokine receptor to GP41


2 ways viruses can penetrate cells

- lipid viruses - can fuse with the host cell membrane and release virus nucleocapsid directly into the cytoplasm - entry via endocytosis


what does the stage of uncoating entail

the release of the viral genome from its protective capsid to enable the nucleic acid to be transported within the cell and transcribed to form new progeny virus


how does HIV penetrate the cell

the hydrophobic region of gp41, once exposed, can initiate fusion of the two membranes


how does virus enter the cytoplasm once inside endosomes

- triggered by low pH of these vesicles --> induces conformational change in the viral proteins that exposes a fusion region - cause lysis of the endosome


where do DNA and RNA viruses usually replicate in the cell - what are the exception?

DNA - in the nucleus - exception poxvirus RNA - in the cytoplasm - exception influenza virus


what is the difference between early and late proteins made by viruses

early proteins are usually non-structural late proteins are usually structural


first thing that virus has to do for replication

translation of nonstructural proteins ( including RNA-dependent, DNA polymerase) --> forms a polyprotein which autocleaves itself


order of genome replication and protein synthesis in viral replication

1. translation of nonstructural proteins 2. autocleavage and further cleavage of polyprotein 3. synthesis of minus strand 4. synthesis of new plus strands


baltimore classes

1. ds DNA 2. - or + ssDNA 3. ds RNA 4. + mRNA 5. - RNA 6. + RNA


where is translation of viral proteins done

by the ribosomes of host cell


what does post-translational cleavage of viral proteins involve

usually needs virus-coded proteases


where does glycosylation of envelope glycoproteins occur

in the RER and Golgi vesicles --> results in their deposition in the cell plasma membrane


assembly of non-enveloped animal viruses - 2 strategies

- spontaneous assembly of capsid proteins around the nucleic acid genome - may require proteolytic cleavage to induce the final conformation in the capsid proteins of the viron


release of non-enveloped animal viruses

only released when virions accumulated in such a number that the cell lyses


how are enveloped viruses assembled and released - 2 strategies

1. budding 2. utilise the secretory pathway


how does budding of virons happen

patches of viral envelope glycoproteins accumulate in the plasma membrane. Capsid proteins and nucleic acid condense direcly adjacent to the cell membrane - the bulges out


types of virus-induced changes in cells

- transformation to tumour cells - lytic infection - chronic infection - latent infection


what are cytopathic effects

morphological changes occurring in cells as a result of infection seen by light microscopy


what is an example of cytopathic effects

inclusion bodies


viral genomes are continually changing as a result of

- mutation - recombination - reassortment


the infectious process can be halted by:

- antibody - blocks uptake and/or neutralises progeny virus - killing the infected cell by cytotoxic T cells, NK cells or Ab-mediated mechanisms - IFN - blocking the replication cycle by specific antiviral drugs


after the initial acute infection, the course of an infection is determined largely by

the immune response of the host --> clearance of persistence


definition of tropism

anatomical localization of infection


routes of entry of viruses

- conjunctiva - respiratory tract - alimentary tract - urogenital tract - parenteral inoculation - skin (via wound)


barriers to infection in the respiratory tract

mucus, cilia, alveolar macrophages, temperature gradients, IgA


what are viruses that infect the respiratory tract that stay localised

- rhinovirus - Respiratory syncytial virus - influenza virus


what are viruses that infect the respiratory tract which spread systemically

- mumps - measles - rubella virus - varicella-zoster


what is receptors of measles virus

CD150 and CD46


what cells does the measles virus infect and what is its route through the body

local macrophages, lymphocytes and DC --> then draining lymph nodes --> then enter circulation and amplify in lymphoid tissue --> then returns to epithelial cells in lung and mouth


what clinical sign is diagnostic of measles

Koplick spots - where the virus is initially replicating - where the lymphocytes are coming in to fight the infection (the spots are the lymphocytes)


barriers to infection in via the alimentary tract

- sequestration in intestinal contents

- mucus

- acidity

- intestinal alkalinity

- proteolytic enzymes secreted by pancreas

- lipolytic activity of bile

- IgA

- scavenging macrophages


what type of viruses tend to survive in the alimentary tract

viruses with multiple capsids that are acid and bile resistant with no envelope


which cells do viruses infect in the alimentary canal

- enterocytes - M cells


action of rotovirus

infect and destroy epithelial cells of the intestinal villi and M cells causing inflammation and diarrhoea. Also secretes NSP4 protein that increases fluid secretion even more


mechanisms of viral spread throughout the body

- local spread on epithelial surfaces - subepithelial invasion and lymphatic spread - spread via bloodstream - viremia - neural spread


primary and secondary phases of viremia

- primary - when virus first enters the blood (only a small amount of virus) - secondary - when it gets to target organ, the virus amplifies and then released into bloodstream again in large loads


what are the three outcomes when viruses infect a foetus

- death and abortion by cytocidal viruses

- developmental abnormalities by non-cytocidal viruses

- immunological tolerance - but a carrier


determinants of viral tropism

- availability of receptors - optimal temperature for replication - stability in extremes of pH - ability to replicate in macrophages and lymphocytes - polarized release - presence of activating enzymes


how can viruses cause host damage

- viral induced damage - consequence of the immune response: --> immnopathology, immunosuppression, autoimmunity


what are the mechanisms of viral-induced damage to tissues and organs

- death of cells resulting directs from viral replication (cyotcidal virus) - death resulting from toxicity of viral products - initiation of apoptosis - loss of function


types of immunopathology caused by viral infection

- antibody mediated pathology - T cell mediated pathology


What is antibody mediated pathology of viral infections

- Ab-dependent enhancement of infection - Antigen-Ab complexes - deposition causes damage


functions of type 1 and 2 interferons against viruses

- inhibits viral replication - activates NK cells (1) Activates macrophages (2) - enhances MHC class 1 expression targets


what produces type 1 interferons when infected by virus?

- macrophages - DC cells - tissue cells


what produces type 2 interferons

NK cells and T cells


what are the 2 main mechanisms for viruses evading the immune system?

- not being recognised - interfering with the functioning of particular immune mechanisms


what is antigenic variation

viruses can vary their surface antigens - allows the virus to escape neutralization by pre-existing antibody


how does antigenic variation arise

arise spontaneously through errors in RNA replication giving rise to point mutations in the genes


what are the targets (and example of the virus) of inhibiting T cell priming by DC

- block cytokine induced maturation of DC (vaccinia and HCV) - interfere with proteins on MHC and costimulatory molecules needed for T cell priming (measles and CMV) - blocks signal transduction from Toll-like Rs (HSV) on DCs - encode a homolog of the cytoplasmic tail of TLRs on DCs


how does the measles and CMV inhibit T cell priming by DC

blocks T cell stimulation - by interfering with the proteins on MHC and costimulatory molecules needed for T cell priming


How does vaccinia virus inhibit T cell priming by DC

- it encodes a homolog for the cytoplasmic tail of TLR4 that inhibits signal transduction to initiate maturation of the DC - blocks cytokine induced maturation of DC


how does HSV inhibit T cell priming by DC

it blocks signal transduction from TLR on DC


how does HCV inhibit T cell priming by DC

blocks cytokine induced maturation of DC


How does HIV evade CD8 T cell recognition

- by making Nef protein - inducing the endocytosis of Class 1 MHC molecules to remove presentation of antigen - antigenic variation of epitope presented by MHC - class 1 MHC gene transcription decreased


which viruses evade the immune system by inhibiting T cell priming by DC

vaccinia, HCV, HSV, measles, CMV


which viruses evade the immune system by evading CD8 T cell recognition

HIV, HSV, CMV, adenovirus, RSV, EBV


how does HSV evade CD8 T cell recognition

HSV protein binds to cytosolic side of TAP transporter and prevents peptide translocation to ER


how does CMV protein evade CD8 T cell recognition

CMV protein binds to TAP transporter on luminal side and prevents peptide translocation to ER


How does adenovirus evade CD8 T cell recognition

- adenovirus protein binds MHC peptide complex and retains it in the ER - class 1 MHC gene transcription decreased


how does EBV evade CD8 T cell recognition

it inhibits the proteosome


how does RSV evade CD8 T cell recognition

decreases the Class 1 MHC gene transcription


function of NK cells

spontaneous cytotoxicity towards a variety of tumour cells and virus-infected cells - major source of IFN-gamma


how are NK cells activated

in response to IL-12 or IFN-alpha/betta


humans with NK cell deficiency are highly susceptible to which viruses

varicella and CMV (herpes virus family)


activation mechanism of NK cells

- activation receptor recognizes molecules on the cell surface that are there as a result of virus infection and will send a killing signal - the inhibitory receptor binds to MHC class 1 molecule on the tarted cell - if engaged will override the killing signal


which virus evade the immune system by affecting NK cell activity and how

human CMV - encodes an MHC class-1 like molecule that is expressed on surface of infected cell and delivers a negative signal to NK cell but cannot itself present peptides to CD8 T cells


what do interferons do to viruses?

inhibits translation of viral proteins by activating PKR - activated by dsRNA


3 ways viruses can escape the actions of interferons

- produces small stretches of RNA that bind to PKR preventing interaction with dsRNA - virus-encoding protein binds to dsRNA preventing PKR activation - virus encoded homologue of eIF2 (translation factor) which competes for PKR inhibiting phsophorylation


outcomes of viral infection

- fatal - full recovery - recovery but permanent damage - persistent infection


typical influenza symptoms

fever/chills cough headache muscle aches fatigue loss of appetite


how long does the flu normally last

~7 days - longer in those who have poor IS


flu spread by

droplet inhalation


incubation and infectious periods of flu

incubation = 1-5 days infectious = 5-6 days


how does influenza bind to cells

HA binds to sialic acid-containing receptors on non-ciliated respiratory epithelium (alpha-2-6 linkage to galactose)


where does influenza multiply

in the epithelial cells of the upper and lower respiratory tract, but particularly large airways


how do you get the symptoms of flu?

IL-1 --> fever IFN--> malaise, headache and muscle aches


how can the flu lead to getting a secondary bacterial infection

viral replication can then go onto to replicate inside ciliated epithelium --> no elevator to stop normal commensals of the URT to move down into the LRT and colonise


structure of influenza virus

- enveloped virus (HA and NA) - has 8 segments of -ve sense ss RNA - Has M1 matrix protein - Has M2 ion channel


what is special about type A influenza

it also infects other species (type B and C don't)


action of HA and NA

HA - has 3 R binding pockets that bind and engage with sialic acid and gets into the cell NA - has 4 subunits that cuts off the sialic acid receptors from the cell surface


how are there different subtypes of Type A influenza

- differ in the form of HA and NA they encode (have similar internal proteins)


what is the ancestral hosts of influenza type A

aquatic birds


current influenza viruses infecting humans

H1N1 H3N2


How does fusion of the endosome with the influenza viral envelope occur

as the endosome becomes more acid - the HA changes conformation leading to fusion --> escape of the 8 viral RNPs


why is tryptase Clara so important in influenza

HA must be cut for the influenza virus to be infectious - this enzyme is only in our RT --> stops it from infecting systemically


if tryptase Clara does not work on influenza, what happens

virus cannot escape the endosome


adaptive immune response to influenza virus

- CD8+ cytotoxic T cells--> kill virus-infected cells - antibody - to HA and NA


what is antigenic drift in influenza virus

mutations and selection of the HA and NA proteins --> pre formed antibodies dont recognise these


targets of vaccine-induced immunity to the influenza virus

- antibody binds to HA - blocking attachment - antibody to NA - blocks efficient release


currently, what does our influenza vaccine contain

H1N1, H3N2 and influenza B


how does the influenza virus give us immunity

induces antibodies (not cytotoxic T cells)


targets of influenza antiviral drugs

1. ion channel blockers - inhibits the function of the M2 ion channel, preventing endosome escape of RNPs 2. NA inhibitors


drug names of antivirals that act on the ion channel of influenza virus

amantadine and rimantadine


drug names of virals that act by blocking the action of NA of influenza

Relenza and Tamiflu


what is antigenic shift?

sudden appearance of an influenza A virus of a new HA (and sometimes a new NA) within the human population


How does antigenic shift cause pandemics?

complete lack of protective immunity --> rapid global spread


why are influenza pandemics rare?

because the virus has to come from birds - where the receptor is alpha-2-3 Gal. Therefore they receptor specificity of the virus has to change before it can affect us


Why are pigs so scary for influenza?

has mixed alpha-2-6 and alpha 2-3 linked SA receptors --> therefore can get coinfection with 2 viruses --> swapping of genes (reassortment) --> infectious to humans


who is particularly susceptible to H1N1 flu

pregnant women obese indigenous populations


what makes an avian influenza virus highly pathogenic

have different cleavage sites that can be cut by an enzyme found in all cells --> systemic spread


Example of viruses that bud out of the cell membrane and are secreted out of the cell membrane

Influenza - Budds out Coronavirus - secreted out


Example of viruses that cause lysis of the cell

Enterovirus, reovirus


What are inclusion bodies

Represent accumulated viral proteins at he site of viral assembly


What is a quasispecies

As a result of mutation, each virus that comes out of a person is slightly different to another infected person


which viruses infect the URT

rhinovirus coronavirus adenovirus measles


which viruses infect the pharnx



which viruses infect the bronchioles

RSV, parainfluenza 3


which viruses infect the alveoli

RSV parainfluenza 3 adenovirus


which virus causes croup



why doesnt rhinovirus spread throughout the RT

because it is unstable at higher temps of the LRT


viruses that infect the GI system but then spread systemically

hep A poliovirus


which viruses if infected during foetal life causes developmental abnormalities

rubella CMV


which viruses can be caught when coming through the birth canal

HSV varicella CMV coxsackie