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171 Cards in this Set
- Front
- Back
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What is the herpesvirus genome like?
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Large, dsDNA in a circle
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How large is the genome?
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125-229 kb
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What the the herpesvirus capsid structure?
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Icosahedral, 162 capsomeres, with surrounding tegument, glycoprotein spikes
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What is the only transcript expressed during latency?
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LAT= latency associated transcript
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What is HHV3?
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Varicella zoster virus
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What is HHV4?
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Epstein-barr virus
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What is HHV5?
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Cytomegalovirus (CMV)
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What is HHV8?
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Kaposi's sarcoma associated virus
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What is the tissue tropism of HSV1 and HSV2?
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Skin and nerves
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What do HSV1 and HSV2 cause?
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Labial and genital disease
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What is the tissue tropism of VSV and what disease does it cause?
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Skin, nerves
-Causes chickenpox and shingles |
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What is the tissue tropism of EBV and what disease does it cause?
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-B lymphocytes
-Causes infectious mononucleosis |
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What is the tissue tropism of CMV and what does it cause?
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-Infects multiple tissues
-Causes perinatal infections -Severe disease in immune compromised hosts |
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What is the tissue tropism of HHV6 and what does it cause?
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-T lymphocytes
-Cause exanthem subitum |
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What is the tissue tropism of HHV7?
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T lymphocytes
-Causes exanthem subitum, reactivation of HHV6 |
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What is the tissue tropism of KSHV?
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-Skin, B cells
-Causes KS in immunocompromised patients |
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What is the difference between HSV-1 and HSV-2?
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They have serologically distinct glycoproteins
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What is the difference in manifestations of HSV-1 and HSV-2?
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HSV-1 causes more: labial infection, ocular keratitis, whitlow, and encephilitis
HSV-2 causes more urogenital infection, menigitis, and neonatal infeciton -Both can cause the other but these dominate as etiological agens |
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Where does latency of HSV1 and HSV2 occur?
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Sensory ganglia
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What can cause reactivation of HSV1 or HSV2?
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Stress, menses, exposure to UV, concurrent infeciton, fever
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What is the medical term for a herpes associated blister?
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Vesicle
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Why is HSV considered an STD?
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To transfer infection, need intimate, warm and immediate contact
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What is the difference between varicella (chicken pox) and zoster (shingles)?
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-Varicella is a result of primary infection, disseminated, enters latency in sensory neural ganglia
-Zoster is a local recurrence of latent infeciton -On one side, and localized to area of intervation |
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How is VSV transmitted?
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Vesicle fluid and respiratory secretions
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What is the incubation period of VSV?
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14-15 days
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What are symptoms of Varicella?
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Fever, chills, myalgia, rash
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What is the difference between Varicella in children, and Varicella in adults?
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Children only have 3-10 vesicles, ill ness is more severe in adults (not uncommon to see >1000 vesicles)
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What is progressive varicella characterized?
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Pneumonia, meninogencephalitis, hepatitis
-Seen in immunocompromised |
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Where does VSV stay latent?
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In the nuclei of cell bodies of the sensory nerves in the posterior root ganglia
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What are the three divisions of the cranial nerves that reach the face?
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- Opthalmic (forehead + eyes)
-Maxillary branch (nose + front of cheeks) -Jaw |
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What is a good way to differentiate between Zoster and Varicella?
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Distribution of lesions - varicella is disseminated and zoster is localized
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What is the difference between the lesions ins mall pox and in chickenpox?
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Chicken pox lesions tend to cluster on the torso and the face and get less frequent as you go towards the extremities
Smallpox has a centrifugal rather than centripetal distribution! |
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What is CMV infection characterized by?
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Ubiquitous but unapparent
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How is CMV transmitted?
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Exchange of infectious bodily fluids (urine, saliva, WBC, semen, vaginal secretions, breast milk, CSF)
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Why is it present in many tissues -yet there is high levels of serum AB?
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Predominately cell-associated (not extracellular)
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When does CMV cause disease?
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-Rare congenital disease in neonates
-Immunocomprimised patients |
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What are some characteristics of CMV syndromes?
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Fever, hepatitis, pneumonia, retinitis, esophagitis, disseminated infection
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What does EBV cause?
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Mononucleosis
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How is it transmitted?
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Oropharyngeal shedding of virus (presence in saliva)
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What is the seropositivity of individuals by age 30?
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90-95% of pop is seropositive by age 30
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What are the symptoms of infectious mononucleosis?
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Fever, sore throat, lymphadenopathy
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What are the signs of infecitous mono?
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Splenomegaly, hepatomegaly, palatal enanthem, jaundice, rash
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What are some lab tests that can use to diagnose EBV infection?
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Increase in mononuclear cells
Atypical lymphocytosis Transient heterophile Ab (Monotest) -Anti-EBV |
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What is the monotest?
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Mixing serum w/ horse RBC- heterophile Ab will aggulinate!
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How is EBV oncogenic?
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Associated with African Burkitt's Lymphoma and Nasopharyngeal carcinoma
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Is EBV sufficent to cause these cancers?
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No usually need another agent
- Genetics - Malaria (Burkitt's) |
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How does EBV infection result in lymphoma?
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-Causes significant polyclonal increase in B cells
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What does the late T cell response do?
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Controls EBV-infected B cells
In patients with T cell defects -we get the progressive B cell lymphoproliferative disease |
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What is indicative of KS-induced angiogenesis?
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Proliferating blood vessels in the skin
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How many types of KSHV are there?
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7 genomic subtypes
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Where does budding of HSV occur?
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At the NUCLEUS!
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SUmmarize HSV life cycle
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-Glycoproteins bind receptors
-Core injected into cytoplasm -Moves to nuclear core - DNA uncoated in nucleus -New nucleocapids constructed IN the nucleus after translatin (proteins go back to nuc!) -Budding at nuclear membrane, transport to ER, Golgi and release at cell surface |
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How does HSV initially associate with the cell membrane?
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Non-specifically by virus glycoprotein C (gC) interacting with proteoglycans on cell surface
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How does the HSV capid get to the nuclear pore?
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Along mictotubules with cell transport machinery
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How does viral DNA uncoating work?
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Viral DNA is injected into the nucleus- capsid proteins remain in the cytoplasm
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When do glycoproteins get inserted into HSV particle?
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Glycoproteins travel in vesicles to cell or nuclear membrane. Viral capids associate with the viral modified membrane via the matrix protein
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How are HSV particles released?
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Via exocytotic vesicles!
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Where is LAT encoded?
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Repeat regions of the genome
Non-protein coding transcript |
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What does LAT do?
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Facilitate reactivation
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What happens to the primary LAT transcript?
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A 2kb intron is spliced, remaining in the latently infected neuron in a circular (latriat) form
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How is LAT thought to facilitate reactivation?
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LAt is thought to prevent apoptosis of latently infected neurons, allowing them to live longer and maintain reactivation potential
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What is the first drug developed against Herpes?
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Acyclovir, short half life, taken every 4 hrs
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What is Valtrex?
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Most sold drug against HSV,
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What is the difference between Valtrex and Acyclovir?
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Prodrug with valine added so that it is stabilized against stomach acid. It is not active, but when the drug is metabolized in the liver, thevaline is removed, converting it to the active form - better deliver system
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What is Famciclovir?
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Modified acycloir
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How does acyclovir act?
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It is a guanisine analog (lacking ribose ring + 3'OH)
-Acts as a chain terminator (lacks 3' hydroxyl) |
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Why is acyclovir such a potent chain terminator?
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Because it lacks the 3'OH, it binds to the HSV DNA pol with MUCH higher avidity
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Why is acyclovir a nucleoSIDE ananlog and not a NUCLEOTIDE analog?
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Cells cannot take up nucleotides. The nucleosides can enter, and then are phosphoryated within the cell that they are going to be used.
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Why does acyclovir work to kill HSV-infected cells SELECTIVELY?
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-Acyclovir is a terrible substrate for phosphorylation by cellular kinases
-HSV 1 and II both express a virally encoded thymidine kinase that is very active at phosphorylating pos1 in acyclovir. Then, cellular kinases can phosphorylate pos 2 and pos3. As a result, DNA synthesis in infected cells only is turned off -because non-infected cells lack this virally encoded TK! |
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Why is acyclovir ineffective against latent infection?
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Thymidine kinase is not expressed in neuronal cells that are latently infected - theonly thing that is expressed is LAT!
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What are two alternative causes of jaundice?
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Hepatocellular injury and cholestasis
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What is indicative of hepatocellar injury?
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Increased levels of intracellular hepatocyte enzymes (ex: aspartate aminotransferase) in the circulation
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How does hepatocellular injury result in increased AST in circulation?
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-Damaged liver cells develop leaky membranes and the enzymes can escape
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What is indicative of cholestasis?
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Increase synthesis of alkaline phosphatase
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How does cholestasis result in increased synthesis of alkaline phosphatase?
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Obstruction of bile ducts (due to biliary obstruction or hepative infiltration) resultsin damage to the bile ducts, resulting in elevated ALP synthesis
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Why is bilirubin not useful to distinguish between cholestasis and hepatocellular injury?
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It may be elevated in both
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What pattern of bilirubin/AST/ALP is charactertic of someone with chronic liver disease?
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Normal bilirubin, elevated AST
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What would the presence of anti-HAV IgM indicate?
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Acute HAV infection
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What would the presence of anti-HBV IgG indicate?
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person is a chronic carrier of HBV
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What does the presence serum HBeAg indicate?
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High virus circulation in the blood
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What is a marker of recovery and immunity to HBV infection?
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Anti-HBs antibody
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Describe a primary hepatocellular carcinoma lesion
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Abnormal liver tissue: partially calcified, multi-lobar, solid mass,
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What is the only treatment for hepatocecllular carcinoma/portal hypertension?
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Liver transplant
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What is required for development of hepatocellular carcinoma?
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Cirrhosis of the liver (liver disease)
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How can acute HBV or HCV infection resolve?
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Clearance of virus from body or development of chronic hepatitis
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What are the outcomes of chronic hepatitis?
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-Remain as mild-moderate disease
-Progress to cirrhosis |
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What can cirhossis progress to?
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-Complications of portal hypertension
-Hepatocellular carcinoma |
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What is the normal surcae of a liver like?
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Smooth
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What are the nodules in nodular cirrhosis composed of?
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Foci of remaining normal liver tissue surrounding by firbotic scar tissue
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What is the difference between the fibrotic scar tissue and normal liver tissue?
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The liver tissue is normally good at regenerating after damage, however, in the case of scar tissue it is permanent and rigid - holding the nodules of normal hepatic tissue in a vice-like grip, and does not let them regenerate or expand
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Does normal liver have fibrous tissue?
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Yes small amounts
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What happens when mild cirrhosis progresses to nodular cirhossis?
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It becomes what is known as bridging cirrhosis - in which foci of scar tissue have joined
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What type of genome does Hepatitis A virus have?
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RNA
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What groups does HAV belong to?
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Picornavirus
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How is HAV transmitted?
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Fecal/oral
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What type of genome does HBV have?
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DNA
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What group does HBV belong to?
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Hepadnavirus
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How is HBV transmitted?
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Blood/sex
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What type of genome does HCV have?
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RNA
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What group does HCV belong to?
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Flavivirus
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How is HCV transmitted?
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Blood
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What type of genome does HDV have?
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RNA
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How is HDV transmitted?
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Blood
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What group does HDV belong to?
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Viroid-like
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What type of genome does HEV have?
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RNA
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How is HEV transmitted?
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Fecal/Oral
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What group does HEV belong to?
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Calcicyvirus
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What is known about HFV?
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Fecal/oral transmission, unknown group, unknown properties
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What type of particles are the HAV particles?
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Icosahedral, unenveloped
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What is thE HAV particle size?
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27-29 nm in diameter
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What are the three morphological forms of HBV particles?
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1) Small, pleomorphic spherical particles (20-22 nm)
2) Tubular 3) 42 nm double shelled virus with cores |
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What type of pattern of infection does HAV, HEV, and HFV follow?
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Acute pattern
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How long is the incubation period for HAV, HEV, and HFV?
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~1 month
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How long do symptoms and jaundice last for in acute HAV, HEV and HFV infection?
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about 6 weeks
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How long does the acute HAV, HEV, and HFV infection last?
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About 0-3 months
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What develops a bit before development of symptoms?
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Elevated liver enzymes (transaminases) and virus presence in feces
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Where are high prevalence areas of HAV?
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Areas in which obtaining clean drinking water is problematic
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How is HAV transmitted in North America?
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Primarily via:
1) Young children in daycare and nursery school 2) highly promiscuous populaions |
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What are some risk factors for HAV infection?
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-Foreign travel
-Personal contact -Outbreak -Daycare -IDU (Intravenous drug users) |
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In which population is the highest rate of HAV attack occuring?
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5-14 yrs old - children serve as a reservoir of infection
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Who is at increased risk of HAv infection?
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Traveleres
Homosexual men Injecting drug users |
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What is the shape of the HBV core?
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Icosahedral
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What envelops the HBV core?
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HBsAg (Hepatitis B surface Ag)
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What is the main component of the HBV core?
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Hepatitis B core antigen (HBcAg)
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What is contained WITHIN the HBV core?
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Hepatitis B e antigen (HBeAg)
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How is the HBV genome arranged?
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Circular, partially-double stranded DNA - neither of the two strands is covaelently complete into a circle
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What is unique about HBV?
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It is a retrovirus!! The viral polymerase (P) has powerful reverse transcriptase activity
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How large is the HBV genome?
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Small - 3221 bp!
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What is the hepatitis B e antigen derived from?
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The core Ag (C) ORF
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What are some risk factors for HBV infection?
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-Promiscuous sex
-Drug abuse -Health care setting -Household contact |
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In which bodily fluids is HBV highest?
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Blood, serum, wound xudates
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Where is HBV moderately detected?
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semen, vaginal fluids
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Where is HBV low/not detectable?
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Urine, feces, sweat, tears, breast milk, saliva
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What is the main means of HBV transmission in high prevalence populations?
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Perinatal
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When does perinatal transmission occur?
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NOT when the baby is in the uterus, but rather transmission occurs at the moment of birth - when the maternal and fetal circulations merge for the first time and there is direct blood contact between the fetus and mother
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Where are the highest rates of chronic HBV carriage?
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Southern China
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When do symptoms appear in an acute pattern of HBV infection?
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About 8 weeks (2 months) post-infection
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Which antigen appears in acute infection?
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HBsAg
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what appears following clearance of acute HBV infection?
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anti-HBsAg
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What happens when HBV infection progresses to a chronic infection?
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-HBsAg increase and stay elevated - never see the appearance of anti-HBsAg
-See anti-HBcAg Abs |
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How does age affect the outcome of HBV infection?
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The age of infection makes a difference - if infections occur at birth - 90% become chronic, whereas if infection occurs in adulthood, only 10% progress to chronic infection
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What are the rugs used to treat chronic HBV infection?
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Nucleoside RT inhibitors:
1) Laminvudine 2) Adefovir 3) Entecavir 4) Telbivudine |
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Can we eradicate chronic HBV infection?
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NO - but we can suppress it to undetectable levels
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What does suppressing HBV to undetectable levels prevent?
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Progression to cirrhosis and liver cancer
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Describe the HCV particle
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Icosahedral, RNA virus
Enveloped - lipid envelope contrains glycoproteins |
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Decribe the HCV genome
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Single stranded, + sense RNA genome - one long ORF
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What are the risk factors for HCV infection?
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-Low socioeconomic group
-Drug abuse -Health care -Sexual/household transmission |
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Describe the presence of HCV RNA in people that develop liver cirhossis and liver cancer as a result of HCV infection
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HCV RNA periodically reappears (gos up and down)
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How big is the HCV genome?
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10 000 nt
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Can we grow HCV in cell culture?
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NO
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how is HCV transmitted primarily?
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Through blood and blood products
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Is vertical transmission a large factor in transmitting HCV?
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No - unlike HBV. It is low but still possible with HCV (~10% of offspring of HCV+ mothers end up infected)
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What percentage of indivudals with acute HCV become chronically infected?
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85%
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What is the "gold standard" of HCV treatment?
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Ribavirin + IFNalpha
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How long is treatment usualyl administered for to clear HCV infection?
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6 months to 2 years
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What is ribavirin?
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Synthetic nucleoside
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What does the HCV genome encode?
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A single polyprotein of ~ 3000 amino acids
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What is NS3?
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Protease encoded by HCV
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What are some protease inhibitors?
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Telaprevir, Boceprevir
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What does NS3 cleave the polyprotein into?
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3 structural proteins:
-Nucleocapsid protein (C) -Envelope glycoproteins - gp33 -gp72 Non structural proteins: -NS1, NS2, NS3, NS4,NS5 |
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What does NS5 encode?
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The HCV Rna-dep RNA pol
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What are some challenges to developing an HCV vaccine?
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-Low immunogenicity
-Characteristics of a protective immune response have been difficult to develop for HCV -variability between isolates (at the nucleotide AND protein level) -HCV mutates easily -No animal model/cell culture system |
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What is unique about HDV?
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It is a defective virus -requires a helper virus to infect humans
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What is the helper virus for HDV?
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Hepatitis B virus
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What does HDV require from HBV?
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The HBsAg to encapsidate its genome
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What is the genome like of HDV?
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Ciruclar piece of RNA
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What is the secondary structure of the HDV RNA genome like?
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Similar to that of plant viroids
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What does the HDV genome encode for?
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Single ORF - encodes both long and short form of the delta-Ag
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What unique activity does the HDV RNA have?
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Ribozyme activity - can self cleave and ligate itself
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What are outbreaks of HEV associated with?
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Fecally contaimnated drinking water
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Which war was HEV outbreak associated with?
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Afghan wars
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