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101 Cards in this Set
- Front
- Back
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General characteristics of Herpesvirus
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Enveloped
Icosahedral capsid dsDNA Pleomorphic Replicates in cell's nucleus Encodes own DNA polymerase and Thymidine Kinase Latency Associated Transcripts |
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What type of genome does Herpesvirus have?
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dsDNA
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What is the shape of Herpesvirus capsid?
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Icosahedral
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Is Herpesvirus enveloped or naked?
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Enveloped
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WHere does Herpesvirus replicate?
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Viral dsDNA
Replicates in nucleus Has its own DNA polymerase and thymidine kinase |
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What machinery is needed for Herpesvirus to replicate?
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Must replicate in cell's nucleus
Encodes its own DNA polumerase and thymidine kinase Necessary to replicate in cells where replication is not occurring (neurons) |
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What happens to the cell following the release of Herpesvirus?
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Cell lysis
No budding involved |
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Latency Associated Transcripts
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LAT
Viral genes that are expressed during the latency period of Herpesvirus It maintains the latent state and helps bring virus out later |
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How does Herpesvirus avoid immune response?
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1. Direct cell-to-cell spread, so no viremia, preventing antibody attack
2. Mimics IL-10 to suppress IFN response 3. Blocks MHC presentation preventing cell-mediated immunity by T-cells 4. Becomes latent so no viral proteins are made |
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How is Herpes Simplex Viruses spread?
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Spread via Direct Contact
Mucosa to mucosa or Childbirth (HSV-2) |
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Which Herpes Simplex Viruses predominately gets transferred during childbirth?
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HSV-2
50% mortality 45% cognitive impairments 5% normal |
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Where does HSV-1 present?
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Associated with oral infections
But 15% cross-over of HSV-2 |
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Where does HSV-2 present?
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Associated with genital infections
But 15% cross-over of HSV-1 |
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How does Herpes Simplex Viruses avoid Immune response?
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1. Cell-to-cell spread prevents verimia and antibody detection
2. Forms syncytia to help cell-to-cell spread 3. Establishes latency in neurons |
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Where does HSV-1 establish latency?
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Sensory Neuron (Trigeminal Ganglion)
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Where does HSV-2 establish latency?
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Sacral/Lumbar Neuron
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What causes Herpes Simplex Virus to reactivate from latency?
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Stress
immune suppression Menstruation UV light Temperature changes |
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Where does Herpes Simplex Virus derive their envelope following replication and assembly?
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Derived from nuclear membrane, not lipid bilayer
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What are some clinical diseases of HSV?
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Herpes Labialis
Herpes Whitlow Eczema Herpeticum Keratoconjunctivitis Encephalitis Primary Herpetic Gingivostomatitis |
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Herpes Labialis
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Caused by HSV (mainly HSV-1)
Cold sores |
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Herpes Whitlow
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Infection on the skin from HSV
Usually due to infection through open wound from the saliva of patients |
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Prevention for HSV
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No vaccine
Avoid contact with lesions |
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Treatment for HSV
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Acyclovir - Guanosine analog that targets thymidine kinase
Becomes incorporated into viral genome stopping DNA synthesis because it terminates the chain Only active in infected cells |
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Acyclovir
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Treatment for HSV and VZV (Varicella Zoster Virus)
Guanosine analog Converted to GMP by thymidine kinase Converted to GTP by cellular kinase Becomes incorporated into viral genome Stops DNA synthesis because new nucleotides cannot be added CHAIN TERMINATOR Works only on active infected cells (not latent ones) |
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How does Varicella Zoster Virus spread?
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Spreads person-to-person by COUGHING/SNEEZING
Only Herpesvirus that transmits this way |
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Where does VZV remain latent?
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Dorsal root ganglia
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What is the clinical manifestation of VZV?
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Chicken pox
Shingles |
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When causes VZV to reactivate from latency?
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Risk of reactivation increases with age
Onset of shingles most common in immunocompromised pts |
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How does Cytomegalovirus (CMV) spread?
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Neonate: Transplacental
Baby: Breast milk, saliva Adult: Sex, transfusion, transplant |
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What is the most common cause of congenital infection?
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Cytomegalovirus (CMV)
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Where does Cytomegalovirus (CMV) remain latent?
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Immune cells including lymphocytes and macrophages
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What causes Mono?
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4/5th of cases EBV
1/5th of cases CMV |
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What is the leading causes of death in HIV infected patients?
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Cytomegalovirus (CMV)
Can cause neuropathy |
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What are the clinical manifestations of EBV?
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Mono
Burkitt's Lymphoma Nasopharyngeal carcinoma |
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What cell does EBV infect?
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Infects B cells
Causes polyclonal hyperproliferation |
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What is the cause of Burkitt's Lymphoma?
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EBV
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How is EBV diagnosed?
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Elevated mononuclear wbc count
Measure heterophile AB agglutination Hairy Leukoplakia in HIV infected pts |
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What is the cause of Mono symptoms?
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Caused by the aggressive T-cell response to the EBV infection and hyperproliferation of B-cells
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Where does EBV remain latent?
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In the throat and blood for life
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What is the cause of Hairy Leukoplakia in HIV patients?
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Re-emergence of EBV
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What is the clinical manifestation of HHV-8
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Kaposi Sarcoma Associated Herpesvirus
See in people with AIDS |
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What causes HHV-8 virulence?
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It inactivates pRb (cellular anti-tumor gene)
Can lead to Kaposi Sarcoma |
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Pol Gene
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Gene in HIV responsible for viral enzymes
Reverse Transcriptase, integrase, protease |
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gp120
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Envelope glycoprotein
Responsible for binding to receptor/co-receptor Causes bystander killing of uninfected cells by causing them to go through apoptosis |
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gp41
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Envelope glycoprotein gene of HIV
Transmembrane protein that is responsible for fusion to cell membrane |
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Vif
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HIV gene
Overcomes cellular intrinsic immunity of APOBEC3B |
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Gag
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HIV gene
Responsible for structural proteins like Capsid |
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What does HIV infect?
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Predominately CD4 T-cells (T-helper cells)
But can also infect Macrophages and DC |
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Where does most of the migration and replication of HIV occur?
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Occurs in Gut Associated Lymphoid Tissue (GALT)
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Where are HIV cells latent?
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Latent in Resting Memory CD4- T-cells
Latency not by choice |
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When can you define full-blown AIDS?
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<200 CD4 T-cells
or <15% of total lymphocytes and/or AIDS defining illness |
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What is the primary screen for HIV?
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ELISA assay
Tests for anti-HIV antibodies Some false positives |
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What is the confirmatory test for HIV
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After ELISA assay
do Western Blot |
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What are some Oral AIDS defining illnesses?
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Candidiasis
Hairy Leukoplakia (EBV infection) Kaposi Sarcoma (HHV-8 infection) |
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Reverse Transcriptase Inhibitor
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Prevents RNA from being converted to DNA
Inhibits Reverse Transcriptase of HIV |
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Protease Inhibitor
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Prevents cleavage of Gag and Pol during budding of HIV virus
Prevents maturation of the viron therefore no longer infections |
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Fusion Inhibitor
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Prevents the fusion of HIV virion to cell membrane
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Integrase inhibitor
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Interferes with HIV virus to integrate its DNA molecule into chromosome
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What antiviral was introduced that dramatically dropped deaths of people with HIV?
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Protease inhibitors
It prevented the cleavage of Gag and Pol enzymes preventing the maturation of the HIV virion Immature virion is not infectious |
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Reverse Transcriptase
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RNA-dependent DNA polymerase
No proofreading activity Error rate is great (10^-4 as compared to 10^-11 of cellular DNA polymerase) |
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Bystander killing of uninfected cells by HIV
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Env glycoprotein gp120 causes apoptosis of cells that are not infected by virus
Reason for immunodeficiency since not many T-cells are killed |
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Long term non-progressors
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LTNP
HIV exposed and uninfected individuals They are associate with a particular MHC allele (Class I B57, B27) that allows them to sustain CD4 cells and maintain lower viral load. |
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Why is there Immune Exhaustion in HIV infection?
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CD8 T-cells initial reduction of viral load
T-cells constantly replicating causing telomere shortening Eventually run out of T-cells CD4 because being killed by CD8 cells and CD8 because can no longer replicate |
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Are all RNA tumor viruses retroviruses?
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Yes
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Are all retroviruses RNA tumor viruses?
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No
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Types of Human Retroviruses
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Some are Tumor causing
HTLV-1 / HTLV-2 - can cause T-cell leukemia HIV-1 / HIV-2 - does not cause cancer directly Spumavirus XMRV |
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Type of DNA tumor viruses
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Herpesvirus (specifically EBV, HHV-8)
Papilloma virus HBV / HCV Adenovirus |
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General classification of Retrovirus
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Enveloped
+ssRNA Has viral RNA-dependent DNA polymerase called reverse transcriptase Integrates into chromosomal DNA |
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Are retroviruses enveloped or naked?
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Enveloped
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What is the genome type for retroviruses
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+ssRNA
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Provirus
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An integrated retroviral DNA genome
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What is the function of Long Terminal repeats in retroviruses genome?
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5' LTR contains promoter
3' LTR contains poly(A) function It mediates integration of the viral genome into the chromosomal DNA |
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Rous Sarcoma Virus
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Retroviruses found in birds
Known to transform normal cells and make them grow indefinitely causing cancer |
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What protein helps mediate fusion of the HIV molecule to the cell?
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gp41 Transmembrane glycoprotein
Encoded in ENV segment |
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What protein helps mediate HIV binding to cell receptors?
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gp120 Outer Docking Glycoprotein
Encoded in ENV segment |
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How can retroviruses cause insertional oncogenesis?
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Activation of c-onc by inserting retrovirus near it
Inactivation of tumor suppressor gene by inserting retrovirus in it |
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General characteristics of Human Papilloma Virus
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Naked
dsDNA Icosahedral capsid Causes genital warts and cervical cancer Sexually transmitted TYpes: 16, 18, 6, 11 |
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How is HPV transmitter?
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Sexual contact
Direct contact |
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HPV infection of cutaneous epithelium
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Local infection
Causes warts |
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HPV infection of mucosal epithelium
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Can cause cervical carcinoma
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What types of HPV cause 70% of cervical cancer?
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HPV 16 and 18
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What type sof HPV causes 90% of genital warts
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HPV 6 and 11
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What HPV types are high risk?
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HPV 16, 18, 6, and 11
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What is the function of E6 and E7 proteins in HPV
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E6 inactivates p53 tumor suppressor gene
E7 inactivates pRb tumor suppressor gene |
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What HPV type is most commonly associated with Oral Squamous Papilloma?
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HPV Type 16
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Oral Squamous Papilloma
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Caused by HPV Type 16
Replicates in skin stem cells Released from dying cells when they are shed |
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Gardasil
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Vaccinates against all 4 types (16, 18, 6, 11)
Given before infection Uses L1 capsid proteins to elicit a antibody response |
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Cervarix
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Vaccinates against HPV 16 and 18
No protection against genital warts HPV 6, 11 |
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General properties of Poliovirus
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Belongs to Picornavirus family
Naked +ssRNA Icosahedral Three serotypes (Poliomyelitis, Polio, infantile paralysis) Transmitted fecal-oral route |
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What type of genome is poliovirus?
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+ssRNA
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Is poliovirus enveloped or naked?
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Naked
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How is poliovirus transmitted?
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Fecal-oral route
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What cells do poliovirus infect?
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Primary site of replication is tonsols/oropharynx/peyer patches
Second infection of motor neurons |
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Polio Vaccines
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Type types
Salk - Inactivated Polio Vaccine -Uses formalin Sabin - Live Attenuated Vaccine Replicated well in gut, but not in nervous system --> but can revert to disease |
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General properties of Arboviruses
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Belongs to family Flavivirus
Enveloped +ssRNA Icosahedral Vector of transmission are arthropods Infections caused by Yellow fever virus, west nile virus, dengue virus |
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What type of genome do arboviruses have?
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+ssRNA virus
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Are arboviruses enveloped or naked?
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Enveloped
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What types of viruses fall under Arboviruses?
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Yellow fever virus
West Nile Virus Dengue virus |
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General properties of West Nile Viruses
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Falls under Arboviruses
Belongs to family Flavivirus Enveloped +ssRNA Icosahedral Vector of transmission are Ares mosquitos BIRDS ARE THE MAJOR RESERVOIR |
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General properties of Dengue Virus
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Falls under Arboviruses
Belongs to family Flavivirus Enveloped +ssRNA Icosahedral Vector of transmission are mosquitos 4 serotypes that USED to be localized HUMANS ARE THE ONLY RESERVOIR |
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Antibody Dependent Enhancement of Infectivity
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Occurs in Dengue infection
Reinfection of a second serotype results in antibodies from the first infection making the second infection worse |