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185 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What type of nucleic acid do viruses have? What do viruses lack that eukaryotic cells have?
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Viruses have DNA or RNA but not both, no ribosomes and no mitochondria
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Describe the lipid membrane envelope of a virus
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it is derived from the host cell membrane, if you have an envelop you have spike glycoproteins
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Which virus has an icosahedral capsid?
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Polio, it's a hard shell w RNA (or DNA for other viruses) wound up
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Give an example of structural and non structural proteins and what relative amounts do viruses make
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Capsid proteins are structural, polymerase proteins are non structural (they're catalytic)
Lots of structural, very few non-structural |
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What does syncytia formation refer to?
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some viruses have an F protein that fuses with cell membranes( Poliovirus)
cell fusion results in Multinucleated cells others include measles, RSV |
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What are viral inclusion bodies?
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A cytopathic effect with Herpes, Cytomegalo, paramoyxo, rabies
so much capsid is produced that material falls out and you see inclusions in the cytoplasm |
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What is the Hemagglutinin Inhibition Assay
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Antibody titer against Influenza, based on ability to bind surfaces of RBCs
If you have antibody, it does not agglutinate |
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The HAI # looks for
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at what serum dilution do you lose the ability to inhibit HA of influenza
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Influenza attaches to ___ for host cell reception
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Sialic Acid
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HIV uses what host cell receptor?
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CD4
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Polio virus uses what host cell receptor?
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Immunoglobulin superfamily
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What is the mechanism influenza uses to get into the host?
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Endocytosis followed by fusion with the endosome
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3 main places for a virus to uncoat
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plasma membrane, within the endosome, at the nuclear membrane
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Spike and glycoproteins get "glued" together by
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matrix protein
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How do non enveloped viruses like adenovirus leave the cell?
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through cell lysis
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Antibodies for Influenza target what step?
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They inhibit virus hemagglutinin to target uncoating
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What does Amantadine do?
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It inhibits Influenza M2 protein which is an ion channel that helps acidify the endosome, with the antiviral it cannot uncoat
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It inhibits influenza M2 protein
M2 is an ion channel that helps acidify the endosome so influenza can uncoat |
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Nucleoside analogs target
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DNA replication
this works for HIV, Herpes |
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Ribaviron targets
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Nucleoside Biosynthesis
works on RNA viruses like RSV |
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How does Oseltamivir (Tamiflu) work?
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It targets the release step of influenza by inhibiting neuraminadase
All viruses then stay on original cell and dissemination is limited |
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What separates the early from late stage?
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DNA synthesis
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In this type of virus the genomic RNA serves as mRNA
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plus strand RNA virus
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Example of +ss RNA virus
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Hepatitis C
+RNA--> - RNA --> +mRNA |
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Example Negative ss RNA
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influenza
goes from -RNA--> +mRNA uses an RNA dependent RNA Polymerase |
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RNA to mRNA breakdown of HIV
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+RNA --> -DNA --> dsDNA --> + mRNA
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Example of a +DNA ss virus
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Parovirus goes from +DNA --> dsDNA --> mRNA uses a DNA dependent RNA Polymerase
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Example of ds DNA virus
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Herpes
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Example dsRNA virus
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Rotavirus
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Phases of DNA virus expression
alpha beta gamma |
Alpha is Immediate Early- regulator
Beta- Early- Enzymes Gamma-Late- structural proteins |
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Do you make structural proteins early or late?
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Late
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Function of Beta Proteins
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promote DNA replicatoin and turn on Gamma mRNA transcription
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Steps of + strand RNS viruses
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1. tranlation by ribosome to large polyprotein
2. polyprotein cleaved by viral and cellular protesases 3. a product, viral polymerase takes the +RNA to -RNA to make progeny genomes |
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2 most common upper respiratory viral infection
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Rhinovirus and coronavirus
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Most common GI vral infections
infants- Children/adults |
Infants- Rotavirus
Children/adults- Norwalk |
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Most common CNS virus for Encephalitis
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Herpes Simplex
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Most common virus to infect Eyes
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Adenovirus
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Heart or Muscle viral infection is most likely
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Coxsackie B virus
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Common cellular respones to virus infection
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Programmed cell death apoptosis
Cytophatic effect of a virus |
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Name virus that infects
motor neurons sensory neurons |
Motor-Rabies
Sensory-Herpes |
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Host Innate Immune response, notices virus in cell because of low class I MHC expression
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Natural Killer cells
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These play a rode in adaptive Immune response to a virus
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T lymphocytes
Cytotoxic T cell and IFN gama for lysis Th1 to activate B lymphocytes |
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Initial host immune response to a virus is
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IFN alpha and Beta
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What host response is the last in response to viral infection
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B cells 1-2 weeks before antiviral antibodis cirulate
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Feature of innate type I interferons
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all bind to common receptor
IFN alph and Beta |
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Type II interferon features
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binds to a separate receptor than type I
IFN gamma comes from activated lymphocytes |
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Most important host reponse during a viral infection
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Interferons
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Explain induction of Interferon response
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Cell notices foreign viral DNA turns on Interferon regulatory factors (IRFs) for type I IFN secretion
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How do IFN type I interact with neighboring cell?
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IFN fits into a receptor on neighbor that activates JAK kinase
-produces a transcription factor for STAT -Interferon Stimulated Genes -Resistant to viral infection |
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What does the NS1 protein of influenza do?
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binds to ds RNA, inhibits host RNA processing, no IFN synthesis
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What does the V protein of Measles do?
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Inhibits STAT signaling, no IFN response
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Herpesvirus makes a 34.5 protein that does what
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counteracts Interferon Stimulated Genes
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Which virus has a protein, ICP47, that inhibits antigen presentation of class I MHC
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Herpes Virus
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DNA dependent DNA polymerase repairs by what activity
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3'-5' exonuclease activity
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Error rate in viral DNA vs RNA polymerase
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Viral RNA polymerase has a really high error rate
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Explain antigenic Drift
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slow accumulation of mutations that result in antibody resistant viruses
Influenza viral spike glycoproteins like HA and NA drift to create new strains |
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Does antigenic drift occur for DNA viruses?
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NO it's DNA polymerase has a low mutation rate
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Reassortment only occurs with
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viruses with more than 1 segment of genome
and must be 2 viruses coinfecting infecting |
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Define antigenic shift
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sudden introduction of new antigenic properties due to a re-assortment of segments (HA and NA for influenza) from 2 different virus strains
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A common example of an 11 segment dsRNA virus that can undergo reassotment, it causes infantile gastroenteritis
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Rotavirus
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Copy-Choice recombination can only happen with ___ and involves what mechanism
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RNA viruses, RNA Pol falls off virus 1, drags RNA it was working on to second virus and finishes synthesizing--> get hybrids
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Copy Choice is common among
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ss RNA viruses
Polio virus new viral genomes that may be drug resistant, antibody resistant, or have new tropism |
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Break-Rejoin only occurs with ___ and involves what mechansim
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DNA viruses,
Nuclease cuts 1 virus and ligase puts it back together with another virus |
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Describe and give an example of complementation
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a defective virus gets help from another wild type virus
coinfection of hepatitis B and D Hep D is defective, Hep B supplies capsid |
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Example of phenotypic mixing
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coinfection where parental viruses mix coats to make mosaic capsid, genomes DO NOT CHANGE
can extend host range |
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Define Interference
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coinfection with one virus negatively influences growth of second
Defective virus competes for limiting components like polymerase |
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Commonly give by killed virus
what are the limitations? |
Polio and Influenza
antibody response high, cell immunity low, requires booster risk of causing disease if not inactivated |
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Live attenuated virus theory and limitations
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Grow virus until achieve desired mutations, it's less virulent
can induce immunity may spread to uninfected people , could revert to wt |
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Theory of subunit vaccines and it's limitation
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produce viron component, example Hep B glycoprotein produced in yeast
antibody response high, cell immunity low |
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What is flumist?
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a reassortment virus given as a live attenuated "vaccine"
it is cold adapted and can only grow in nose |
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A provirus is
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an integrated DNA copy of virus genome (term used for retrovirus)
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For retroviruses unspliced mRNA codes
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GAG and POL
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For retrovirus spliced mRNA can create
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ENV
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What does gag encode for retrovirus
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matrix protein
Capsid Nucleocapsid Protease to cleave gag and pol |
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What does pol encode for retrovirus
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Reverse Transcriptase (RNA dependent DNA Pol)
Integrase |
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What does env encode for retrovirus?
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Surface proteins
transmembrane proteins |
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In retrovirus how do you get Gag and Pol?
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Normal translation produces Gag
A slippery sequence produces Gag+Pol 99% of time get Gag 1% of time get Pol |
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How is env obtained in retroviruses?
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mRNA splicing produces env
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Small amounts of ___ are found in a mature virion
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Protease, Reverse transcriptase, and integrase
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Retrovirus assembly
how do Env proteins get to surface what happens to viral genome |
Env proteins TM-SU go from ER--> Golgi-->Plasma Mem
Viral genome synthesized by cellular polymerase and forms dimer in cytoplasm (bc its 2+strand RNA) |
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How do viral oncogenes differ from cellular?
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Only contain portion of cellular oncogene
Do not contain splice sites Are separated from normal controls |
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What is a transducing oncogenic retrovirus
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After recombination virus and host, the viral genome encodes an oncogene that was grabbed from host
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What is a non-transducing oncogeneic retrovirus
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recombination into genome next to an oncogene, the transcription factor of the virus activates the oncogene
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Some tranducing retroviruses like avian myeloblastosis have this
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an oncogene instead of the viral gene Myb instead of ENV
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RSV parainfluenza measles and mumps are what type of virus
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paramyxovirus, negative strand RNA
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Type of virus that influenza is
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orthomyxovirus, negative strand RNA
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Transport of Influenza to the cytoplasm requires
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NS2 protein
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Rinoviruses and coronaviruses are both postitive or negative RNA or DNA?
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Positive RNA viruses
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Viral pneumonia/ bronchitis likely caused by
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Parainfluenza and RSV
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Influenza changes every 2-3 years due to Antigenic Drift or Shift?
The major antigenic changes with severe epidemics are a result of Antigenic Drift or Shift? |
Every couple years- Drift
Epidemics- Shift |
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Features of Orthomyxoviruses
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-RNA virus, segmented genome, envelope, helical nucleocapsid
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Hemagglutinin has a role in
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Attachment- binds sialic acid
Penetration- mediates fusion of virus envelope with endosome |
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Gene expression of influenza is usual patter for -RNA virus with what unusual feature?
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takes place in nucleus of cell
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Antigenic drift does not change
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H or N subtype
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How do new H subtypes of influenza occur?
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Antigenic shift
reassortment between genome segments of human and animal |
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Zanamivir and Oseltamivir target
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Neuramidase in influenza, not much resistance
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Amantadine and Rimantidine target
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Ion channel M2 in influenza, high incidence of resitance
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Paramyxoviruses are
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Negative RNA virus, nonsegmented, enveloped, helical nucleocapsid
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How do RSV and Parainfluenza enter a cell
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fusion of virus envelope with plasma membrane mediated by F protein
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Where does replication occur for RSV and parainfluenza
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in the cytoplasm (no mRNA splicing)
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HIV belongs to what group of retroviruses?
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lentivirus
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Name genetically distinct groups of HIV and which is most common
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M,N,O
M for major N non major O outlier |
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Lentivirus infections feature this type of mutation and genetic diversity
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lots of mutation bc no prrof reading and copy-choice recombination
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A simple retrovirus contains __ copies of what kind of RNA
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2 copies of + sense ssRNA
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Describe what happens to gb160 precursor of HIV
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gets glycosylated and knicked in Golgi to make gp41 and gp120
gp41 is a fusion protein gp120 i sa receptor binding domain |
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HIV gb120 uses
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CD4 receptor
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What are the coreceptors for HIV
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CCR5- macrophages and CXCR4-T cells
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Features of HIV using the R5 virus
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slow replication and non-syncytia
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Features of HIV using X4 coreceptor
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usually a more mature virus, it rapidly replicates, lots of syncytia and rapid T cell death
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What is the likely cellular reservoir for HIV latent infection?
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In the lymph nodes follicular Dendritic cells chronically infected
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Progression of Acute to Chronic to Clinical symptoms of HIV
describe what happens to macrophages and T cell |
macrophage carriers latent or low viron, gets activated, can disseminate (could go to brain, see demintia) or can stimulate latent-->extensive infection in T cells see loss of CD4
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Name 2 important auxilliary proteins in HIV and what they do
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Tat and Rev
modify host machinery for proper environment |
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Name an important late auxilliary protein for HIV and what it does
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Vpu- makes structural proteins, improve infectivity
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In trascription of HIV what is the default path?
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splicing
this makes mRNA for Tat Rev and Nef |
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Unspliced HIV produces
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gag, pol, env
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What is the role of Rev protein of HIV?
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RNA binding protein that binds to rev-response element RRE to control splicing
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What is the role of Tat of HIV?
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RNA binding protein binds Tat-associated RNA element RAR to enhance transcription
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Describe what happens with or without Rev in HIV transcription
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No Rev results in Rev,Tat, Nef
Rev + mRNA inhibits splice to make gag/pol or have 1 splice for env |
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What does HIV protein Tat do?
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Tat binds the HIV TAR sequence to promote better processivity of cellular RNA polymerase
it ensures that the full length genome gets made |
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What is the job of VPU in HIV?
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inhibits the host protein tethrin which tethers progeny to plasma membrane
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What is tethrin?
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An interferon inducible protein that prevents HIV release
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How does AZT work?
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Its a reverse transcriptase inhibitor nucleoside derivative
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How does Neveripine work
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Its an RT inhibitor non nucleoside analog
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Saquinavir works by
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inhibiting viral protease
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Enfuviritide works by
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glycoprotein inhibitor blocks gp41
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Name hepatitis transmitted by: fecal-oral route
blood |
Fecal-oral: A E
Blood: B C D |
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Describe Hepatitis A
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positive sense RNA virus, w a shell and RNA for polyprotein and protease
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Describe immunity to HepA
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get long term immunity after first infection or vaccine, no chronic infection, only 1 serotype
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Diagnose acute HepA infection by appearance of
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HAV IgM in serum
see this about a week before symptoms start |
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Describe structure of HepB
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contains complete +DNA w partially incomplete -DNA
Viral RNA attaches to plus end to act as primer |
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HBV lifecyle
Viral DNA goes to nucleus and gets converted to |
Covalently closed circular (CCC) DNA
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CCC DNA of HBV makes ____
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2 types of RNA
short transcripts and a long full pregenome |
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The short transcript of HBV goes to the ___ and makes ____ which has ability to ___
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Golgi
S protein, a surface antigen SA SA can bleb of independently without matrix ext |
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The full length protein of HBV makes
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2 proteins
Capsid and P protein P protein is Reverse Transcriptase (RNA dep DNA pol) |
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Difference between retroviral RT and HBV RT
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In retrovirus RT works early in life in nucleus
In HBV RT works on outgoing virus |
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Key markers of acute HBV infection First see, then
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First see Anti HBsAg to surface antigen then see anti-HBc IgM, response to core protein
the core protein response will persist for life the surface antigen response wanes after infection passes |
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Markers of chronic HBV infection
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both HBsAg and HBc IgG persist at high levels for life
Patient is negative for IgM HBc and positive for HBsAg in serum |
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Compare the immunological profile of 2 patients immune to HBV one who had a vaccine and one who had a previous infection
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Both have - serum HBsAg
Vaccinated Patient: -anti cAg + anti sAg Previous infection: + for anti cAg + for anti sAg |
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Serum levels of what mark an HBV infection currently going on ___ interestingly you will not see ___
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HBsAg
won't see anti-sAg in serum because all is complexed with HBsAg |
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Treatment for HBV
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Interferon alpha
Lamivudine- nucleoside analog inhibitor of RT |
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Hepatitis C has what kind of genome?
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+ RNA
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Outcome of an Hep C infection depends on
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T cell response
if robust T cell response may clear it |
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Persistant infection of HepC even in presence of anti-HCV antibodies because
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E2 glycoprotein has hypervariable region, lots of mutants
E1 is the other glycoprotein |
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Hepatitis D encodes
must have___ also |
Hepatitis Delta Antigen only
Needs Hepatis B to help, cannot cause infection alone |
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HepD genome
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ss ciruclar RNA
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lytic herpes infections take place in
Latent ones? |
lytic- mucosal epithelial or cloes to mucosa
latent- long lived cells neurons/ memory lymph/stem cells |
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Herpes genome is
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large ds DNA
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Where are alpha herpes viruses latent?
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sensory neural ganglia
simplex viruses are in this category |
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Alpha Herpes Viruses cause
1 2 3 |
HSV1- cold sores
HSV2- Genital ulcers HHV3 is VZV chicken pox and shingles |
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Beta Herpes viruses (3 of them)
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HHV5- Cytomegalovirus, mono
HHV6- roseola, infants HHV7 like CMV |
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Gamma Herpes Virus
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HHV4 Epstein Barr- mono, lymphoma, carcinoma
HHV8 Kaposi's sarcoma |
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These diseases are worse in adulthood than childhood
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Varicella zoster virus and Epstein Barr
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Herpes can counteract immune system during lytic infection by___
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degrading/blocking MHC class I antigen presentation
Sequestering C3b and IgG Expressing Bcl2 to avoid apoptosis Block IFN alpha |
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What response if critical to clear Herpes?
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Effective T cell response
this is why it is so severe in immunocompromised |
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Where do HSV1, HSV2, and VZV establish latency
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in sensory neural ganglia
HSV1- trigeminal ganglia HSV2- sacral ganglia VZV- dorsal root ganglia |
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Reactivation of alpha HV based on
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trauma, fever, stress, taking glucocorticoids
anything that causes immune suppresion |
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What is the significance of Thymidine Kinase
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enzyme expressed by herpes virus (HSV1,2, VZV and EBV) that is required to produce DNA precursor
many prodrugs take advantage of this and require viral TK to become active |
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Antiviral prodrugs that require Herpes TK for activation have good activity on active Herpes infections, why do they not work on latent infections?
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In latent infections the virus uses cellular DNA Pol to maintain genome instead of viral DNA Pol
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Acyclovir will not work on
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CMV
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How is the chicken pox vaccine given?
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live attenuated VZV
means it could spread to other hosts |
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Why might you see high rate of shingles in communities with high VZV vaccination rate
? |
individuals with natural VZV infections have T cells that are not boosted with exposure throughout adulthood
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Leading cause of infectious birth defects
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Cytomegalovirus
only if primary infection during pregnancy |
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What is relation between Epstein Barr Virus and B cells?
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Viral gene products drive B cells into memory B
Latent membrane proteins do this |
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EBV latent membrane protein 1 action
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mimics signal from helpter T cell to drive B cells to memory cells
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EBV infections reside in
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memory B cells
get symptoms bc cytokines and T cells try to clear the infected B cells |
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How can EBV cause cancer?
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NOT caused just by viral infection
only happens if host is immune compromised or cellular mutations promote transformation |
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How does Burkitt's lymphoma happen
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B cell origin
Chomosomal translocation of c-myc gene under control IgG promotor this rapidly triggers cell death viral apoptotic proteins rescue the cell and allow tumor growth |
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Kaposi sarcoma is a cancer of
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endothelial cells
its a gamma herpes virus |
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latency of the beta herpes viruses
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hematopoeitic stem cells
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Role of pRb
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Retinoblastoma
keeps E2F sequestered and inactive free E2F makes lots of cell division |
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what is p53
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tumor supressor gene
keeps p21 in check initiates Bax cell death if inappropriate dividing |
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What kind of virus is human papillomavirus
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small
non enveloped stable 80 serotypes |
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HPV cervical carcinoma highest risk types____
HPV skin carcinoma highest risk |
Cervical- 16 18
Skin- 5, 8 |
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HPV virus infects
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basal cell
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How does viral DNA of HPV replicate in terminally differentiated cells?
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uses cellular polymerase it DOES NOT have viral DNA Pol
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Pathology cell changes in HPV for cervical carcinoma
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see large nucleus, more cytoplasm, quilocytotic cells
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What is the role of E7 protein in HPV
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binds pRb and releases E2F
high risk forms have great affinity and ability to induce pRb degradation |
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What is the role of E6 HPV protein?
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Modifies ubiquitin ligase E6AP
E6AP targets p53 for degradation blocks cell death |
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Normally E6 and E7 get turned off in HPV, what keeps them turned on?
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Viral integration into host genome may keep E6/E7 on
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What strains of HPV does Guardasil target?
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16, 18 (cervical cancer) along with 6,11
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JC virus
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progressive multifocal leukoencephalopathy
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BK virus
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nephropathy in renal transplant setting
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MC virus
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Merkel cell carcinoma
small, non eveloped, skin cancer of mechanoreceptor cells |
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How does Merkel Cell carcinoma progress?
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viral large T protein inhibits pRb and p53
viral genome gets integrated and replication is defective |
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What does Adenovirus cause?
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influenza like repiratory epidemics conjunctivitis, gastoenteritis, tonsilitis
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E1A protein of Adenovirus targets
E1B target |
pRb to release EF2
p53 degradation |
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