topic 8: viruses Flashcards
what are viruses defined as and why?
- defined as non-cellular infectious particles
- because they do NOT consist of cells (do not fit the definition of a living organism)
what is the approximate size of viruses?
10 - 300 nm diameter
define viruses
obligate intracellular parasites:
- depend on the host cells for their replication
- use enzymes of the host cells in order to replicate
what are the characteristics of viruses?
- obligate intercellular parasites
- can infect both eukaryotes and prokaryotes
- bacteriophages
- important pathogenic agents in both animals and plants
what are bacteriophages (phages)?
viruses that infect only prokaryotes (bacteria)
compare the sizes of eukaryotes, prokaryotes, and viruses
virus - 0.05μm
phage - 0.1μm
bacterium - 1-10μm
eukaryotic cell - 10-100μm
** bacteria is around 10-100x smaller than eukaryotic cells
** viruses are much smaller than both prokaryotic & eukaryotic cells
what is the essential structure of a virus? what is an additional structure that some viruses have?
essentially made from:
(1) nucleic acid (DNA or RNA)
(2) a protein capsid
additional structure:
(3) envelope (an external protective layer)
what is a capsid? what is it responsible for?
- a protein coat
- encapsulates the nucleic acid and protects the viral genome from nucleases
- may have fibers that assist the attachment of the virus to the host cell
what is the function of an envelope? what does it consist of?
- consists of membrane
- carries glycoproteins
- is required during the exit of viruses from cells that they infect
- only present in enveloped viruses
viral genomes may consist of?
- single or double-stranded DNA
- single or double-stranded RNA
what are the 2 types of viruses that can exist based on the type of nucleic acid they contain?
- DNA viruses
- RNA viruses
capsids are built from protein subunits called?
capsomeres
what are the types of shapes or symmetry that a capsid can have?
- icosahedral (spherical) symmetry
- helical symmetry
regarding viral capsid structures, what type of capsid structure do each of the following have:
(1) tobacco mosaic virus (TMV)
(2) adenoviruses
(3) influenza viruses
(4) bacteriophage T4
(1) non-enveloped, helical capsid
(2) non-enveloped, icosahedral capsid
(3) enveloped, helical capsid
(4) non-enveloped, icosahedral capsid
what type of nucleic acid do each of the following have:
(1) tobacco mosaic virus (TMV)
(2) adenoviruses
(3) influenza viruses
(4) bacteriophage T4
(1) RNA virus
(2) DNA virus
(3) RNA virus
(4) DNA virus
most animal viruses are _____, unlike most plant viruses which are _____
- enveloped
- non-enveloped
ALL phages are _____
non-enveloped
what does the viral envelope contain?
viral glycoproteins which bind to specific receptor molecules on the surface of the host cell
what function does the viral envelope help with?
- it helps the virus infect their host cells
- envelope fusion with host cell membrane
what is the origin of viral envelopes?
they are derived from the host cell’s membranes (mainly the plasma membrane but can be the nuclear membrane)
how does specificity of a bacteriophage work?
different types of phages infect specific different bacteria types
when is the viral envelope formed?
- during the exit of the viral particles from the host cells
- therefore, they contain a combination of viral and host cell molecules
describe the structure of a phage
- capsid head
- protein tail
what is the function of the phage capsid head?
encloses their nucleic acid (commonly DNA)
what are two contributing factors in the differences in both replication and transcription processes in viruses?
(1) enveloped vs. non-enveloped viruses have differences
(2) DNA viruses vs. RNA viruses have differences
what is the function of the phage protein tail?
has fibers that facilitate the attachment of the phage to the host cell
what does it mean for viruses to be obligate intracellular parasites?
they can only replicate within a host cell
what are the stages of the viral replicative cycle?
SOSS
(1) attachment
(2) penetration (entry of virus into cell)
(3) uncoating (of viral genome)
(4) replication
(5) gene expression
(6) assembly
(7) release (exit)
(8) maturation (only for enveloped viruses)
what are some differences in the replicative cycles of enveloped vs. non-enveloped viruses?
- penetration into the host cell
- release from the cell
describe the virus life cycle
- viruses are infectious particles that take over the operation of a cell to manufacture new viruses
- they are very specific in the type of cells they infect
- they use the pattern of protein receptors on a cell’s surface to target cells for infection
- in the case of a DNA virus, it is rather simple compared to the DNA inside a host cell, only containing the info needed to manufacture new virus parts
- once inside, the instructions in the DNA are transcribed to RNA, the protein-making machinery then translates this into the components of a new virus
- once new viruses are assembled, when ready they emerge from the cell, killing it
- some retain parts of the host membrane, forming an envelope around themselves (enveloped viruses) for protection
- every new virus is capable of infecting another host cell, repeating this process
regarding virus specificity, what do viruses depend on in their ability to infect a specific cell?
the type of cell-surface receptors of the target cell
what do anti-viral drugs do in regards to the viral life cycle?
they target points in the life cycle of the virus, preventing it from replicating
describe step (1): attachment of the virus to the host cell, in both enveloped and non-enveloped viruses
SOS
- enveloped viruses: glycoproteins on the viral envelope attach on receptors on the plasma membrane of the host
- non-enveloped viruses: fibers or spikes on the viral capsid attach on the host cell membrane
describe step (2): viral entry to the host cell (penetration), in both enveloped and non-enveloped viruses
SOS
- enveloped viruses: mostly by membrane fusion (of the viral envelope with host cell plasma membrane)
- non-enveloped viruses: by endocytosis
describe step (3): uncoating of the viral genome
SOS
capsomeres fall apart
(catalyzed by lysosomal enzymes)
what processes does step (4): virus replication in the host cell include?
- replication of the viral genome in the host cell
- replication of the viral proteins in the host cell
there are different replication mechanisms for viruses based on?
their viral genome type
what are the 4 types of viruses based on their nucleic acid?
- double stranded DNA viruses (ds DNA)
- single stranded DNA (ssDNA)
- double stranded RNA (ds RNA)
- single stranded RNA (ss RNA)
what type of RNA has 3 types? what are they?
single stranded RNA viruses have 3 different types:
- positive sense RNA genome (5’ - 3’ RNA) viruses
- negative sense RNA genome (3’ - 5’ RNA) viruses
- retroviruses
what are retroviruses?
- a type of ss RNA virus
- has positive sense RNA genome (5’ - 3’)
- replicate through the enzyme reverse transcriptase (converts RNA to DNA)
describe the replication of viral genome process (of step 4) in the host cell for DNA vs RNA
SOSSSSSS
DNA viruses:
- use the same mechanisms as the host cells (have the same genome as us)
- ss or ds viral DNA replicates using the host DNA polymerase
- viral DNA replicates using host DNA polymerase to produce viral cDNA (multiple copies)
- cDNA = copy DNA
RNA viruses:
- use different mechanisms than the host (cannot use our enzymes)
- all RNA viruses use the same enzyme, except retroviruses
- retroviruses use the viral enzyme reverse transcriptase to produce viral cDNA, THEN use the host RNA polymerase to produce the viral RNA copies
- other RNA viruses (+ and - sense) use the viral enzyme RNA-dependent RNA polymerase to replicate and produce viral RNA copies
describe the viral protein production process (of step 4) in the host cell (transcription + translation) for DNA vs RNA
SOSSSSSS
DNA viruses:
- viral mRNA is produced from viral DNA using the host cell RNA polymerase
- viral DNA uses hot RNA polymerase for transcription to produce viral mRNA, then uses host cell ribosomes to produce viral proteins (translation)
RNA viruses:
- the viral RNA serves as either:
(i) mRNA (positive sense RNA viruses)
(ii) as template for production of viral mRNA (negative sense RNA viruses) using viral RNA-dependent RNA polymerase
- this is because viruses with a 3’ - 5’ RNA genome need to be converted into their complementary strand (5’ - 3’) to serve as mRNA
- as for translation, the viral mRNA is translated into the viral proteins using the host ribosomes and the translation machinery of the host cell
- (+ sense): viral RNA –> produce viral proteins using ribosomes
- (- sense): viral RNA –> viral mRNA using RNA-dependent RNA polymerase –> produce viral proteins using ribosomes
what is the only process taking place in RNA viruses where the host machinery is used?
translation
compare host and viral enzymes
(1) host DNA polymerase:
- DNA dependent DNA polymerase
- uses DNA as a template to synthesize a new DNA strand
- DNA –> DNA
(2) host RNA polymerase:
- DNA dependent RNA polymerase
- uses DNA as a template to synthesize a new RNA strand
- DNA –> RNA
(3) viral RNA polymerase:
- RNA dependent RNA polymerase
- uses RNA as a template to synthesize a new RNA strand
- RNA –> RNA
- used by (+ and - sense) RNA viruses to replicate their viral genome
- used by ONLY (-) sense RNA viruses to produce their viral proteins
(4) viral reverse transcriptase:
- RNA dependent DNA polymerase
- uses RNA as a template to synthesize a DNA strand
- RNA –> DNA
- used by retroviruses to replicate their viral genome
describe step (5): viral assembly
- the viral proteins (capsomeres) assemble to produce the new capsids
- the capsids then encapsulate the new viral genomes to produce the new viral particles
describe step (6): viral release (exit) from the cell, in both enveloped and non-enveloped viruses
- enveloped viruses: released by budding, then acquire an envelope through a process called maturation
non-enveloped viruses: released by lysis of the host cell using lysosomal enzymes
(the membrane breaks open and the new viral particles are released)
how is the host cell destroyed after the release of the virus?
- the change in permeability of the plasma membrane (due to the presence of the viral proteins)
- inhibition of the host cell gene expression (the virus “steals” the host enzymes), the cell has no more machinery to do its own protein synthesis, and dies
what is the only exception to the central dogma of transfer of genetic information?
retroviruses
- retroviruses dogma: RNA –> DNA –> RNA –> protein
what is an example of a retrovirus, and what disease does it cause?
SOS
- HIV (human immunodeficiency virus)
- HIV is the retrovirus that causes AIDS (acquired immunodeficiency syndrome)
what type of cells does HIV infect?
T helper cells, also known as CD4
describe the retrovirus replicative cycle
SOS
(1) attachment and entry: the viral glycoprotein (gp120) binds to host cell receptor (CD4)
(2) reverse transcriptase: viral enzyme converts the viral RNA into cDNA
(3) integrase: viral enzyme integrates the viral genome into the host genome => the retrovirus cDNA produced is inserted (integrated) at random into the host genome as a provirus
(4) the host’s RNA polymerase transcribes the proviral DNA into RNA molecules
(5) the viral RNA molecules function:
- as mRNA for synthesis of viral proteins
- as genomes for new virus particles released from the cell
(6) protease: viral enzyme cuts and cleaves the viral polypeptide produced by translation => enables assembly and release from the cell
(functional proteins need to be cleaved)
what is a provirus?
the genetic material of a virus as incorporated into, and able to replicate with, the genome of a host cell
what are the 3 viral enzymes?
SOS
the retroviral RNA genome encodes for three enzymes essential for virus replication:
(1) reverse transcriptase: responsible for the conversion of the single-stranded genomic RNA into double-stranded proviral DNA
(2) protease: converts the immature virion into a mature virus through the cleavage of precursor polypeptides
(3) integrase: inserts the proviral DNA into the host cell genome
what is integrase?
- an enzyme found in HIV (and other retroviruses)
- HIV uses integrase to insert (integrate) its viral DNA into the DNA of the host CD4 cell
viruses do not consist of cells, are not classified as microorganisms, but as ?
pathogens
what is believed to be the origin of viruses?
SOS
nucleic acid fragments released
what are the possible sources of viral genomes?
plasmids, bacterial and yeast DNA, transposons (small mobile DNA segments)
what is pathogenicity?
the ability for organisms to cause pathogenic diseases
what are the different mechanisms where viruses may damage or kill host cells?
(1) cause the release of hydrolytic enzymes from lysosomes => cell lysis
(2) cause the infected cells to produce to toxins that lead to disease symptoms
(3) have toxic macromolecules (e.g. such as envelope proteins) and/or change the permeability of the plasma membrane (due to the presence of vital proteins)
(4) inhibition of the host cell replication machinery
what is cell lysis?
the destruction of the plasma membrane so that the viruses are released
which of the mechanisms of virus pathogenicity applies to only non-enveloped viruses?
viruses causing the release of hydrolytic enzymes from lysosomes => cell lysis
which of the mechanisms of virus pathogenicity applies to only enveloped viruses?
having toxic macromolecules and/or changing the permeability of the plasma membrane
which of the mechanisms of virus pathogenicity applies to both enveloped and non-enveloped viruses?
- causing the infected cells to produce toxins that lead to disease symptoms
- inhibition of the host cell replication machinery
what are vaccines?
harmless derivates of pathogenic microbes that stimulate the immune system to mount defenses against the harmful pathogen (to produce antibodies)
what do vaccines commonly consist of?
of dead or inactivated pathogens or their products (e.g. proteins/nucleic acids)
why are vaccines important?
- important control measure as viral infections cannot be treated by antibiotics
- vaccines can prevent certain viral illnesses (and certain bacterial illnesses)
what are emerging viruses?
those that suddenly become apparent
what are examples of emerging viruses?
(1) the 2009 flu out break (pandemic) caused by the influenza virus strain H1N1
(2) the current COVID-19 pandemic by the coronavirus SARS-CoV-2
what are flu epidemics caused by?
new strains of influenza virus to which people have little immunity
how can new viral diseases emerge?
- when viruses spread from animals to humans
- viral strains that jump species exchange genetic material with other viruses to which humans have no immunity
what can these new strains cause?
pandemics (global epidemics)
what is an example of a pandemic caused by a virus spread from animals to humans?
the 2009 flu pandemic was likely passed to humans from pigs => it was originally called the “swine flu”
what is SARS-CoV-2?
- severe acute respiratory syndrome coronavirus 2
- the virus strain that causes the respiratory illness named Coronavirus Disease 2019 (COVID-19)
what type of virus is SARS-CoV-2?
an enveloped positive-sense ssRNA virus
what is the zoonotic origin of SARS-CoV-2?
current hypothesis is to have passed from bats via an intermediate host to humans
what are the only currently approved antiviral drugs?
- remdesivir
- molnupiravir
-paxlovid (nirmatrelvir +ritonavir)
describe COVID-19
- Corona Virus 2019
- common symptoms: include fever, cough, fatigue, shortness of breath, loss of smell + taste, loss of appetite, sputum production, muscle & joint pain
- complications: pneumonia, multi-organ failure, or cytokine storm
- transmission: air-borne (via respiratory droplets)
what are the diagnostic methods involved in COVID-19?
(1) real-time reverse transcription polymerase chain reaction (rRT-PCR)
(2) antigen tests (rapid tests/self tests)
describe the mechanism of rRT-PCR
- from a nasopharyngeal swap sample
- includes viral particles => viral RNA detection
- amplifies the viral cDNA to produce many copies
- highly sensitive method as it detects viral DNA (detects viral nucleic acid NOT the viral capsid protein)
describe the mechanism of antigen tests
- viral antigen detection from nasal/nasopharyngeal swab
- detects viral proteins (surface glycoproteins)
- not as sensitive as it doesn’t multiply the viral protein
which method is more likely to produce false negatives?
antigen tests
how does PCR amplify viral DNA to produce many copies?
- viral RNA –> reverse transcriptase –> cDNA –> DNA polymerase –> cDNA (35-40 copies)
- first detects viral RNA with a non-viral enzyme (reverse transcriptase in this case is not viral, as COVID is not a retrovirus)
- reverse transcriptase converts the viral RNA to DNA which is amplified using DNA polymerase
- both reverse transcriptase and DNA polymerase are commercially available
what types of treatment for COVID-19 are there?
(1) anti-viral drugs
(2) anti-inflammatory drugs
(3) neutralising antibodies
what are the types of anti-viral drugs used for COVID-19 treatment?
(1) remdesivir - the USA and UK gave Emergency Use Authorization for it in critically ill COVID-19 patients
(2) molnupiravir - was also approved by them only for cases where remdesivir cannot be used (ex: patients with severe asthma)
(3) paxlovid - approved use in EU
(4) other antiviral drugs under clinical trials
what is the mode of action for the anti-viral drugs remdesivir and molnupiravir?
viral RNA polymerase inhibitors-nucleoside analogues
- inhibit viral RNA polymerase
- block viral replication
what is the mode of action for the anti-viral drug paxlovid?
Pfizer protease inhibitor
- blocks the protease in COVID
- which inhibits post-translational modification
IF anti-viral drugs are not sufficient, we
proceed with using anti-inflammatory drugs and neutralising antibodies
what are the types of anti-inflammatory drugs used for COVID-19 treatment?
(1) dexamethasone
- corticosteroid drug with anti-inflammatory and immunosuppressive function
- used for patients requiring oxygen support only
what drug would you give a COVID patient with serious condition, requiring oxygen support?
dexamethasone
what are the types of vaccines used for COVID-19?
(1) Pfizer/Moderna
(2) Novavax
(3) Johnson & Johnson/Astra Zeneca
(4) Valneva
which of the COVID-19 vaccines are considered new technology?
Pfizer, Moderna, Johnson & Johnson, Astra Zeneca
what is the mode of action in Pfizer/Moderna vaccines?
mRNA vaccines
- use the host cell ribosomes & translation machinery to produce viral proteins, and the immune system recognizes foreign antigens and produces antibodies
what is the mode of action in Novavax vaccine?
protein subunit
- includes the actual viral surface glycoproteins, and also causes antibody production
- old technology
what is the mode of action in Johnson & Johnson/Astra Zeneca vaccines?
vector vaccines
- carrying viral genes
- carry COVID-19 DNA (SARS-CoV-2 DNA) with transcription converted into mRNA, with translation converted to protein, then leading to formation of antibodies
what is the mode of action in Valneva vaccine?
whole inactivated virus vaccine
- they cheat our immune system to think we are infected, to produce antibodies
what are the major human viral diseases?
- adenoviruses
- coronaviruses
- rhinoviruses
- enteroviruses
- herpesviruses
- ebola virus
- human immunodeficiency virus (HIV)
- human papilloma virus (HPV)
- poliovirus
- mumps, measles, and rubella viruses
- hepatitis viruses
- influenza virus
- prions
what are the major human viral diseases that cause common cold?
adenoviruses, coronaviruses, rhinoviruses, enteroviruses
what do herpesviruses include?
(1) Herpes simplex viruses (HSV-1 and HSV-2)
(2) Varicella Zoster virus (VZV)
(3) Epstein-Barr VIrus (EBV)
(4) Cytomegalovirus (CMV)
what do Herpes simplex viruses cause?
HSV-1 : oral infection (blisters; cold sores)
HSV-2 : genital infection (blisters; genital sores)
what does Varicella Zoster virus cause?
- causes chicken pox (in children)
- shingles (herpes zoster in adults)
what does Epstein-Barr virus cause?
- causes infectious mononucleosis (kissing disease)
- may also cause Burkitt’s lymphoma and nasopharyngeal carcinoma
what does cytomegalovirus cause?
causes CNS infections (hearing loss, encephalitis)
what does ebola virus cause?
hemorrhagic fever (fatal)
what does human immunodeficiency virus (HIV) cause?
causes AIDS
what does human papilloma virus (HPV) cause?
- cervical warts (types HPV-16 / 18)
- genital warts (benign papillomas; types HPV-6 / 11)
what type of transmission causes HPV?
sexually transmitted disease
what are the prevention measures used for HPV?
(1) vaccination
- vaccine Gardasil (HPV 16/18/11/6)
- vaccine (HPV 16/18)
(2) pap test
- cervical smear => detection of morphological abnormalities
- e.g. cervical dysplasia
what does poliovirus cause?
poliomyelitis
what are the prevention measures used for poliovirus?
Sabin or Salk vaccines
what do mumps, measles, and rubella viruses cause?
mumps, measles, and rubella respectively
what are the prevention measures used for mumps, measles and rubella?
MMR vaccine
what do hepatitis viruses cause? (what is hepatitis)
liver inflammation
what are the two major forms of hepatitis?
(1) acute hepatitis => jaundice
(2) chronic hepatitis => cause liver cirrhosis and hepatocellular carcinoma
what are the major hepatitis viruses?
(1) hepatitis A virus (HAV)
(2) hepatitis B virus (HBV)
(3) hepatitis C virus (HCV)
describe hep A virus
- type: RNA virus
- transmission: food-borne
- vaccine: available
describe hep B virus
- type: DNA virus
- transmission: blood, other biological fluids (sexually transmitted)
- vaccine: available
describe hep C virus
- type: RNA virus
- transmission: blood or sexually
- vaccine: NOT available, not developed yet
how does HIV infect the body?
- infects the T-helper lymphocytes
(T h-cells) - viral glycoprotein gp120 attaches to the CD4 receptor on the surface of T-helper cells
- causes AIDS
what are two ways AIDS is manifested as?
(1) opportunistic infections
- e.g. candidiasis, toxoplasmosis, pneumonia
(2) malignant tumors (cancers)
- Kaposi sarcoma: malignant tumors of the epithelial cells of the blood vessels
- Burkitt’s lymphoma: B-cell cancer
what are the different transmission types of HIV?
- sexual intercourse (through sperm/vaginal fluids)
- blood (e.g. by infected needles/syringes, blood transfusions)
- mother to child (during pregnancy, birth or breast feeding)
describe the detection of HIV
- window period: the virus cannot be detected yet (due to the low levels in the blood) but can still be transmitted to other people
- detection: the virus can be detected in blood 3-6 weeks after window period (suspected infection date) depending on the detection method
what are the diagnostic methods with HIV?
- detection of anti-HIV antibodies in the blood using ELISA (6-8 weeks after infection)
- detection of viral RNA in the blood using RT-PCR (3 weeks after infection)
what are the therapeutic strategies used with AIDS?
- no cure for HIV
- no vaccine due to high mutation rates of virus
treatment strategies: - HAART: highly active anti-retroviral therapy, which is a combination of different types of antiretroviral drugs
what are common problems associated with antiretroviral drugs?
toxicity, resistance
what are the antiretroviral drug types used in AIDS?
(1) nucleotide analogues
- inhibit the viral RNA replication by being incorporated into the growing cDNA chain
(2) non-nucleotide analogues
- inhibit the activity of reverse transcriptase
(3) protease inhibitors
- inhibit the HIV protease which is responsible for the viral polypeptide cleavage and hence the maturation of the virus particles
what is an example of a nucleotide analogue antiretroviral drug used in AIDS
AZT (azido-deoxy-thymidine)
- the next nucleotide cannot be incorporated into the growing DNA chain due to the presence of nitrogen (N3) instead of -OH
=> inhibits the viral RNA replication
what is polymorphism of HIV?
it mutates at a very very high rate
what are non-conventional viruses?
viruses that do not have the characteristic virus structure
(capsid + nucleic acid), so they lack one or the other
what are viroids?
- viruses without a protein capsid (only contains nucleic acid)
- infectious nucleic acids that replicate in tissues
=> plant pathogens (mostly)
what are prions?
- viruses without nucleic acids (PROTEINS only)
- small infectious proteins that replicate in tissues
=> animal pathogens
describe viroids
- small circular RNA molecules
- infect plants => disrupt their growth
describe prions
- slow-acting indestructible infectious proteins
- prions propagate by converting normal proteins into the prion version => aggregation in tissues
- causes: serious CNS infections (spongiform encephalopathies)
what are examples of prion diseases?
- Scrapie disease in sheep
- mad cow disease
- Creutzfeldt-Jakob disease in humans
what does a “prion version” of a normal protein entail?
a different 3D conformation
describe mad cow disease
- infects cattle (e.g. cows)
- transmitted to humans by consumption of contaminated beef (COOKING DOES NOT DESTROY THE PRIONS)
- causes Creutzfeldt-Jakob disease (CJD) in humans
describe Creutzfeldt-Jakob disease
- fatal CNS infection by prions
- symptoms: ataxia, memory less, convulsions, coma
