Virology Flashcards
1
Q
Viral envelope: influenza virus
A
- Hemagglutinin: surface glycoprotein, attaches to sialic acid residues of host cell surface
- Neuraminidase: surface spike, aids in release of virus from host cells
2
Q
Viral proteins: matrix proteins
A
- links envelope and capsid: stabilisation
- can drive final assembly process
- important determinant of budding location
- viral capsid is made of proteins, which assemble without E requirement
- Capsids can be icosahedral or helical
- Icosaheral viruses have 20 facets (each an equilateral triangle. and 12 vertices, which results in 5- 3- and 2-fold symmetry.
- All known human viruses w helical capsids are naked.
3
Q
DNA viruses
A
- Enveloped (dsDNA)
- Pox
- Herpes
- Hepadna
- Naked capsid (dsDNA)
- polyoma
- papilloma
- adeno
- parvo
4
Q
RNA viruses
A
- RNA
- Naked
- Picorna
- Calici
- Enveloped
- Toga
- Flavi
- Corona
- Naked
- RNA
- RNA
- Enveloped
- Rhabdo
- Filo
- Orthomyxo
- Paramyxo
- Bunya
- Arena
- Enveloped
- RNA
- +/- RNA
- double capsid
- reo
- RNA via DNA
- Retro (enveloped)
- RNA via DNA
5
Q
Baltimore classification of viruses: Class I
A
- Class I: dsDNA
- Papilloma, polyoma, herpes, adeno, pox
- some can transform cells
- host enzymes transcrobe IE or E mRNA
- E-proteins: replicate parental DNA & late (L) mRNA;
- L-proteins: assemble into capsids
- Capsids: incorporate the viral DNA to make mature virus
6
Q
Class II
A
Class II: ssDNA
- very small (parvum=small), circo- or parvo-virus (linear so susceptible to DNAses)
- replication occurs in nucleus
- form a (-) strand -> template for (+) strand
- require cell enzymes
- mRNA translated into viral proteins
- NOTE: no immediate early or early proteins
- viral proteins: make up capsids
- viral DNA is encapsidated in progeny virus
- Parvovirus can only replicate when cells are actively replicating
- icosahedral, non-enveloped
7
Q
Class III
A
Class III: ds RNA Virus
- dsRNA: cannot function as mRNA; class III must package an RNAP to make mRNA after infection of host cell
- genomes segmented
- RNA-dependent RNAP in virion
- Ex. Reo-, Birnaviruses, rotavirus
- ds RNA -> transcribed to viral mRNA (v-mRNA) by virus-associated RNA-dependent RNAP
- v-mRNA: translated to structural and non-structural proteins:
- viral proteins to form immature capsid
- mRNA packaged into immature capsid, then copied w/in capsid to form ds RNA
- Rotaviruses, members of Reoviridae
- acute gastro in infants and young children
- icosahedral
- 11 dsRNA segments
- RNA replication: concurrent w packaging of genome segments
8
Q
Class IV
A
Class IV: (+) sense RNA viruses
- Divided into IVa & IVb
- always infectious w/o viral proteins
- ends of genomes often modified w caps
- Ex. Picorna-, toga-, corona-, flaviviruses, dengue
IVa
- polyprotein: post-translational cleavage make multiple viral proteins
- non-structural proteins: transcribe parental (+) RNA into (-) RNA whih in turn is transcribed to (+) RNA
- Structural proteins: make up capsids, incorporate viral RNA - progeny virus
IVb
- stuctural proteins (not one polypeptide)
- parental RNA transcribed into (-) RNA by viral non-structural proteins
- ss (-) RNA -> transcribed into (+) RNA (many copies)
- Capsid incorporates the (+) RNA, other viral proteins -> progency virus
IV: Picornaviruses
- naked, small, icosahedral
- genome is mRNA (naked genome is suffcient for infection)
- virus replicates in cytoplasm, most are cytolytic
- v-RNA: translated into polyprotein; cleaved into enzymatic & structural proteins
- include poliovirus, hepA, rhino- and enteroviruses
9
Q
Class V
A
Class V: ss (-) sense RNA viruses
- more diverse than + sense, larger
- segmentation common
- genome by virus-specfic polymerase (premade); reads (-) RNA -> forms (+) RNA
- assembly of capsid -> incorporation of genomic RNA and viral proteins, including the virus RNAP -> progeny virus
- Ex. Filiviruses, Orthomyxo-, Bunya- (Hantavirus), Paramyxo-viruses
10
Q
Class VI
A
Class VI: ss (+) sense RNA viruses (RT)
- 2 copies of +ve strand RNA (not ds); premade RT generates ds provirus
- retroviruses (HIV)
- Provirus: integrates into host genome, template for synthesis of viral mRNA
- Viral mRNA: viral non-structural and viral structural proteins
- not directly infectious on its own
- Non-structural proteins: may be RT and other polymerases
- Structural proteins: assemble into the capsid
- Mature virion: the capsid incorporates viral genome AND the nucleoproteins including RT -> progeny virus
11
Q
Class VII
A
Class VII: ds DNA viruses, ssRNA intermediate, RT
- Ex. Hepadnaviruses (HBV)
- VII: partially ds DNA virus comes in w its own RT
- core is stripped of nucleic acids
- fills in gaps
- ds supercoiled DNA
- pre-genomic RNA
- structural proteins made and then assemble into a capsid
- pre-genomic RNA goes into capsid; this is ss
- maturation: RT makes a RNA-DNA hybrid in capsid
- RNAase activity digests RNA
- DNA polymerase activity makes the partially dsDNA
- comes out of Golgi and goes out of cell
- VII: HBV
- enveloped virion w partially ds circular DNA genome
- replication is thru a circular RNA intermediate
- virus encodes and carries RT
- HBV has a strict tissue tropism to liver
- HBV genome can integrate into host chromosome
12
Q
Defective virus
A
- complete virus particle BUT unable to replicate w/o helper virus (lacks full complement of genes for complete lifecycle)
- Ex. Hep D requires Hep B to replicate
13
Q
Pseudovirions
A
- contain non-viral DNA, infectious but do not replicate
14
Q
Viroids
A
- infectious, subviral particles
- small, circular ssRNA genomes
- mainly cause plant diseases
- Hep D appears to be a viroid-lke entity (enclosed in Heb B)
15
Q
Virophage
A
- Sputnik: 18 kb circular ds DNA, icosahedral virus (50 nm)
- grows only in a strain of mimivirus w/in infected amoeba
16
Q
Host defenses
A
- non-specific
- interferon
- Type I: IFN-alpha & beta
- Type II: IFN-gamma aka macrophage activation factor
- complement
- other cytokines
- interferon
- specific
- Ab production
- specific immune system
17
Q
Immunopathology
A
- immune response to viral infection can cause tissue injury, i.e. group specific Ab from previous infection actually protect virus.
- Ex. CMV (circulating immune complexes -> depositis -> arthritis)
- Ex2. Dengue (hemorrhagi shock sydnrome: fixation of complement by circulating immune complexes -> release of products via complement cascade -> sudden increase in vascular perm, shock, death
18
Q
Persistent infection & latency
A
- Persistent infection: Ex. Adenovirus; not totally resolved so certain number of viruses constantly produced; infection w/o cell death, selection of ideal target cell subsets (chronic - nonlytic, productive); viruses apply numerous avoidance strategies to persist
- direct selective pressure to suppress infected host’s innate and/or adoptive immune system
- viruses can alter/interfere w the processing of viral peptides by professional APC
- can downregulate co-stimulator and/or MHC molecules (required or T cell signaling)
- inhibit the differentiation of dendritic cells; infect effector T and B cells directly.
- Latency: virus goes there and hides even when host is healthy; recurrent infection;
- modulation of viral gene expression
- viral subversion of cell apoptotic pathways
- avoidance of clearance by immune system
19
Q
Basic steps of viral disease
A
- acquisition
- initiation of infection at primary site
- incubation period (amplification, spread to secondary site)
- replication in target tissues
- immune response (limit & contribute)
- transmission
- resolution or persistent infection
20
Q
Site in Viral Disease: GIT
A
GIT: Ex. Rotavirus (class III)
- no sx -> gastroenteritis, vomiting, diarrhea
- transmission: fecal, especially in daycare, resp. possible
- At risk:
- Infants < 24 mo
- Older children & adults: at risk for mild diarrhea
- Undernourrished
- Rotavirus resistant to environmental and GI conditions
- asymptomatic infection -> virus release
*
21
Q
Sites in viral disease: Exanthems & hemorrhagic fevers
A
- virus-induced skin disease
- major classifications of viral rashes
- macules: spots
- papules: raised
- nodules: larger raised
- vesicular lesions: blisters containing virus
- hemorrhagic fevers -> infect endothelial cell lining of the vasculature, possibly compromising the structure of bv
22
Q
Organ example: HBV
A
- enveloped virion w partially ds, circular DNA genome
- replication is through a circular RNA intermediate
- virus encodes and carries RT
- HBV has a strict tissue tropism to the liver
- HBV genome integration into host chromosome
23
Q
Sites in viral disease: CNS
A
Ear infections and blood infections spread to brain
Ex. encephalitis, viral meningitis,
Ex. Herpes producing cerebral hemorrhage
24
Q
HHV-1 & HHV-2: CNS & STI example
A
- Both HHV-1 &-2 (HSV-1 & 2) large ds DNA enveloped icosahedral virus
- can initially infect and replicate in mucoepithelial cells
- lytic (most cells: Cowdry type A inclusion bodies, syncytia)
- persistent (lymphocytes & macrophages)
- latent infections (neurons)
- virus blocks effects of interferon, prevents CD8 T-cell recognition of infected cells, escapes Ab neutralisation and clearance by going into hiding during latent infection
- Latency in CN V and then triggered.
25
HHV-5 (CMV): eye
* Pink eye due to adenovirus (HHV-5) infection
* chorioretinitis associated w CMV in newborns
* most prevalent viral cause of congenital disease
* Affected newborns show:
* small size, thrombocytopenia, microcephaly, intracerebral calcification, jaundice, hepatosplenomegaly (HSM), and rash
26
Examples of viruses transmitted in blood
* Hep B, C, G, D
* HIV
* HTVL-1
* HHV-5 (CMV)
* HHV-4 (EBV)
* W. Nile encephalitis virus
27
Host cell changes in response to viral infection: Cytopathic effects (CPE)
* rounding
* inclusion bodies
* Ebola virus inection: liver inclusion bodies
* GI hemorrhage due to CMV: stomah
* cell lysis, necrosis, apoptosis
* syncytia formation
* transformation
* Giant cells
*
28
Cancers due to viral infections
* HPV -\> cancers of cervix & oral cavity
* HBV & HCV -\> HCC
* EBV -\> Gastric cancer, nasopharyngeal carcinoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma
29
Tumour viruses: Transformation
* loss of growth control
* reduced adhesion
* motility
* invasion
* ability to form tumours
* Transformed cells frequently exhibit chromosomal aberrations
* Lytic stage -\> Late proteins
Transformed -\> early proteins -\> stopped -\> then undetectable
30
Early function proteins are involved in transformation
* Papilloma: oncoproteins E6 & E7
* E6 modifies p53 & hTERT
* E7 modifies pRB
* Polyoma: large T and small T antigen
* polyoma virus have ds circular DNA
- both early and late proteins expressed during lytic
- only late proteins expressed in transformation
* Adenovirus: E1A and E1B
* BK virus: Large T
* SV-40: Large T
31
EBV (HHV-4)
* \>90% of EBV-infected people intermittentl shed the virus for life (even asymptomatic)
* approx. 70% of the US population infected by age 30
* causally associated w endemic Burkitt's lymphoma (AfBL), Hodgkin disease, nasopharygneal carcinoma (NPC)
* has 3 potential outcomes:
* replicate in B cells or epithelial cells permissive or EBV replication
* cause latent infection of B cells in presence of competent T cellls -\> Downey cell association (atypical T cells, enlarged cell & nucleus)
* stimulate and immortalize B cells
* Note: both B- & T-cells required for antigenpresentation
32
HHV-8 (KSHV): Kaposi's sarcoma
* tumour of bv wall
* rare in people not infected w HIV
* common in HIV+ people frequently detected tumour in AIDS Pt
* pink, red, or purple lesions on skin and mouth
33
Merkel cell polyomavirus (MCV)
* Merkel cell carcinoma (MCC) highly aggressive neuroendocrine carcinoma of skin w a high propensit of recurrence and metastasis
* 5-year disease-specific survival rate ~60%
* MCV associated w most MCC cases (subset of MCC, 20 - 30%, do not harbour MCV and apparently have a distinct pathoetiology)
34
Hep B (DNA)
* each of the hepatitis viruses infects and damages the liver
* classic sx of jaundice and release of liver enzymes
* spread by blood or needles, sex, and perinatally; also in tears, semen, vaginal.
* median incubation period of ~ 3 mo, after which icteric sx start
* chronic hep follows in 55 to 10%
* 1/3 of world's pop has been infected w HBV -\> 1 to 2 million deaths/r
* incidence of HBV is decreased (development, use HBV vaccine)
* strict tissue tropism to liver
* HBV produces HBx protein to regulate apoptosis, proliferation, genetic instability to stay in host liver and produce small amounts of virus continuously
* can integrate into host chromosome
35
HCV
* HCV transmission -\> develop cancer 10 to 50 years (median 30 years)
* flavivirus (class IV) w (+) ss RNA genome
* Exception: only flavivirus not transmitted thru insects
* continual liver repair, induction of cell growth during chronic HCV infection
36
RNA tumour viruses
* some retroviruses have oncogenes in addition to regular genes
* retroviruses - particularly oncovirinae
* Ex. HTLV-1 -\> leukemia
* cause cancer after \>30 y latency
* promote cell growth in more indirect ways than oncogene-encoding viruses
* associated w non-neoplastic neurologic disorders and other disease
* adult acute T-cell lymphocytic leukemia (ATLL) & HTLV-1 associated myelopathy (tropical spastic paraparesesis)
* Tax: transcriptional regulator -\> activates promoters including IL-2 & IL-2R
* integrates near cell growth-controlling genes
37
Non-Hodgkin's lymphoma
* viral infections: HTLV-1, Hep C, and EBV, increase the risk of developing non-Hodgkin's lymphoma
38
Hep C (RNA)
* produces the following proteins:
* core to regulate apoptosis
* NS2 -\> proliferation
* N55B -\> genetic instability
* HCV transmission -\> develop cancer: 10 to 50 years (median 30 years)
* HCV is a flavivirus (class IV) w a (+) ss RNA genome
* Exception: only flavivirus not transmitted thru insects
* acute HCV infection can go 3 routes:
* Recovery & clearance (15%)
* Cirrhosis rapid onset (15%)
* Persistent infection (70%) of which 40% asymptomatic leading to chronic hepatitis, further leading to
* liver failure
* cirrhosis
* Primary hepatocellular carcinoma (PHC)
39
Viral vaccines: attenuated
* altered (mutated) to non-pathogenic form
* tropism altered -\> no longer grows at a site to cause disease
* Polio (Sabin), MMR, Yellow fever, Rotavirus, Varicella
40
Viral vaccines: inactivated
* rendered non-pathogenic usually by chemical treatment such as w formalin that cross-links viral proteins.
* Ex. Hep A, Influenza, Polio (Salk)
* influenza vaccine: trivalent inactivated vaccine (TIV), however live attenuated vaccine is more effective
41
Viral vaccines: subunit
* Virus Like Particles (VLPs)
* HepB
* Quadrivalent HPV 6/11/16/18 L1 VLP (Gardasil)
* HPV vaccine
* Recombinant L1 proteins that self-assemble into VLPs
* Admin. before onset of sexual activity, then 2x after (~100%) protection from infection w vaccine HPV types.
* Potential to prevent ~70% of cervical cancers, ~90% of genital warts.
42
Viral vaccines: DNA
2 ways:
- take viral DNA, circularize into plasmid, plasmid coated w gold particles and injected
- take viral gene and splice into another vector. ex. vaccinia virus
43
Viruses treatable w antivirals
Herpessimplexvirus
• Varicella-zostervirus
• CMV
• HIV
* Influenza A and B viruses
* RSV
* HBV & HCV
* Papillomavirus
* Picornavirus
44
Targets for antiviral drugs
1. Recognition & attachment: Ab-receptor antagonists
2. Uncoating: Amantadine, Arildone, Rimantadine, Tromantadine
3. Transcription: interferon, antisense, oligomers
4. Replication: nuceloside analogues (guanosine), AZT, Acyclovir
5. Protein synthesis: interferon
6. Fusion: Tromantadine, Enfuvirtide
7. Assembly: protease inhibitors
45
Antivirals: blocking viral replication
nucleoside analogues: incorporated into viral genomes -\> inhibition of function of viral DNAP.
* chain termination: analouges lack hydroxyl groups for linking of backbone,
* Ex. Acyclovir for HHV-I & HHV-II: Guanosine analogue, must undergo TK-mediated phosphorylation (Acyclovir triphospate)
*
* Nucleoside inhibitors of RT
* Ex. AZT
* Ex2. ddl
*
* Non-nucleoside polymerase inhibitors
* Ex. Nevirapine binds to various sites on enzyme
46
Antivirals: blocking assembly and release
* Ex. protease inhibitors (Saquinavir)
* block cleavage of polyproteins
* HIV is dependent on proteolytic enzyme for full infectivity
* Drug-resistant strains \> protease mutations
47
Control of viral diseases: immunomodulators
* Interferons:
* IFN-alpha: active against many viral infections (Hep A, B, and C, HSV, HPV, and rhinovirs)
* Imiquimod
* TLR ligand, stimulates innate responses to attack the virus infection (HPV)
48
Rationale behind antiviral cocktails
CART & Highly Active Antiviral Treatment (HAART)
- multiple mechanisms to control viral diseases
