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72 Cards in this Set
- Front
- Back
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What is the protein coat of a virus and what does it do?
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capsid that encloses the genome and determines shape of virus
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Where does a virus get its envelope and what is it?
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-membrane stolen from infected cell (plasma or cytoplasmic membrane)
-lipid bilayer w/ associated glycoproteins -surrounds the protein capsid |
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What are the basic shapes of viruses?
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spherical or rod (helical)
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What determines the shape of a virus?
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Shape determined by arrangement of subunits of capsid that encloses the genome
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What is the viral genome?
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DNA or RNA
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How do viruses replicate?
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-produce mRNA to be used as template for protein
-translate numerous copies of these viral proteins making more virions so that they proliferate |
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What are viruses?
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-obligate, intracellular parasites
-cannot generate energy or produce proteins INDEPENDENT of a host cell -cannot replicate outside a host cell |
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What kind of environment does an enveloped virus prefer?
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fluid environment (ex: influenza - lower respiratory airway)
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What kind of environment does a naked capsid virus prefer?
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less dependent on fluid -> relatively resistant to drying (ex: rhinovirus - upper respiratory airway)
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What are some clinical classifications of viruses?
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hepatitis, respiratory, enteric, exanthems, STDs
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Where do RNA and DNA viruses usually replicate?
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RNA - cytoplasm
DNA - nucleus |
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What are the steps in Viral Replication?
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1) ATTACHMENT of viral attachment protein to cellular receptor (glycoprotein)
2) PENERATION via direct fusion at plasma membrane or receptor mediated endocytosis 3) UNCOATING 4) VIRAL PROTEIN SYNTHESIS (regulatory, then structural proteins) and VIRAL GENOME REPLICATION 5) ASSEMBLY into mature virion 6) RELEASE via cell lysis (and lipid membrane acquisition for enveloped viruses) |
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Why must the cell be metabolically active for penetration to occur during viral replication?
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The virus crossing the cell membrane to access the intracellular machinery needed for virus replication is an ENERGY-DEPENDENT process.
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What are the different ways that a virus can enter the cell to replicate?
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1) DIRECT FUSION of plasma membrane - not pH dependent
-only enveloped viruses 2) RECEPTOR MEDIATED ENDOCYTOSIS - pH dependent (low pH) -enveloped - fusion with endosome (ex: influenza) -naked capsid - endosomal lysis |
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In what order are the viral proteins made during viral replication?
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First regulatory proteins (polymerases, integrase, protease) used in genome replication and production of individual proteins.
Second structural proteins (proteins of capsid and envelope) |
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When does complete assembly occur for most non-enveloped viruses and for enveloped viruses during viral replication?
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non-enveloped - before it is released from the cell
enveloped - still acquires lipid membrane as virus buds through cell membrane (budding may or may not lyse the cell) |
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How does virus release occur during viral replication?
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release occurs via cell lysis
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Where are the VAPs for enveloped and non-enveloped viruses?
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VAPs (virus attachment proteins)
enveloped - on envelope surface (envelope/spike proteins) non-enveloped - on capsid, usually at most exposed points on the surface |
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What determines virus tropism and what is it?
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viral attachment proteins - determine what kind of cells are infected by different viruses.
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What is the VAP for the influenza A virus and what virus family is it in?
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HA (hemagglutinin)
orthomyxoviridae |
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What in particular do some anti-influenza agents block?
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the HA VAP
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What dictates HIV tropism?
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The CD4 receptor and chemokine co-receptor on the Helper T cell.
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Describe the DNA viral genome.
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-1 copy of DNA (haploid)
-dsDNA (except parvoviruses is ssDNA = 'part-of-a-virus') -linear or circular -icosahedral -replicate in nucleus -large DNA viruses (ex: herpesviruses) have repeated sequences and introns |
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What features of DNA viral replication makes them so virulent?
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-some DNA genomes can be read in ALTERNATIVE READING FRAMES allowing a single sequence to encode overlapping genes
-both strands of some DNA viruses can be transcribed in a LEFTWARD or RIGHTWARD direction allowing for multiple genes to be encoded in a small stretch of DNA |
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What is unique about papovaviruses replication?
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circular DNA so can be transcribed in leftward or rightward direction allowing for multiple genes to be encoded in a small stretch of DNA
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Describe the RNA viral genome.
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-1 copy of RNA (haploid)
-ssRNA or dsRNA -circular or linear -ssRNA can be defined by sense/polarity |
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What is the difference between a plus/positive sense or minus/negative sense RNA virus?
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Plus sense - same sequence as mRNA so can serve as mRNA (except retroviruses)
Minus sense - complementary sequence to mRNA (all minus have envelopes) |
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What is the most efficient type of virus?
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ssRNA, positive sense
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What must negative/minus sense RNA viruses have to replicate?
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RNA-dependent RNA polymerase that copies the negative stranded genome into plus sense RNA upon infection
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What RNA virus is ambisense?
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Hantavirus (one part is plus sense, one part is minus sense)
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Why do RNA viruses have a high degree of genetic diversity?
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-They LACK REPAIR mechanisms for RNA polymerase.
-Some viruses have SEGMENTED GENOMES that REASSORT when cells are co-infected with different clones or subtypes (ex: influenza). -considerable SECONDARY STRUCTURE that may affect gene expression and replication |
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Genome, Source, Incubation Time, Diagnosis, Treatment, Prevention, and Chronicity of Hepatitis A (HAV)
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Genome - ssRNA
Source - feces (fecal-oral) Incubation Time - 25 (15-40) days/4wks Diagnosis - IgM/IgG detection Treatment - supportive Prevention - pre/post exposure immunization Chronicity - none |
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Genome, Source, Incubation Time, Diagnosis, Treatment, Prevention, and Chronicity of Hepatitis B (HBV)
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Genome - dsDNA
Source - blood/blood-dervied body fluids Incubation Time - 75 (30-150) days Diagnosis - +HBsAg Treatment - 3TC (epivir); interferon, adefovir Prevention - pre/post exposure immunization Chronicity - 20% |
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Genome, Source, Incubation Time, Diagnosis, Treatment, Prevention, and Chronicity of Hepatitis C (HCV)
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Genome - ssRNA
Source - blood/blood-derived body fluids Incubation Time - 50 (15-120) days Diagnosis - HCV RNA Treatment - interferon, ribavirin Prevention - blood donor screening; risky behavior modification Chronicity - 45% |
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Genome, Source, Incubation Time, Diagnosis, Treatment, Prevention, and Chronicity of Hepatitis D (HDV)
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Genome - ssRNA
Source - blood/blood-derived body fluids Incubation Time - 35 (25-50) days Diagnosis - HDV RNA Treatment - none Prevention - pre/post-exposure immuniztion; risky behavior modifcation Chronicity - 10% |
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Genome, Source, Incubation Time, Diagnosis, Treatment, Prevention, and Chronicity of Hepatitis E (HEV)
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Genome - (+)ssRNA
Source - feces Incubation Time - 40 (20-55) days Diagnosis - no commercial test Treatment - supportive Prevention - ensure safe drinking water Chronicity - none |
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Which hepatitis viruses are only acute and which can be chronic?
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A,E - acute
B,C - chronic ??? |
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Which hepatitis virus can lead to a fatal outcome if infected during pregnancy?
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HEV
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Where is Fulminant Liver Failure mostly seen?
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with HBV (only a small % of acute HBV infections progress this far)
-very rarely occurs after acute hepatitis |
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What is Fulminant Liver Failure?
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hepatic failure within 8 weeks of onset with encephalopathy, coagulopathy, and massive hepatic necrosis on liver biopsy
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What are some Signs and Symptoms of Acute Icteric Hepatitis?
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-may be asymptomatic (occurs right at onset of symptoms if symptoms occur)
-symptoms: fatigue, malaise, abdominal pain in RUQ, nausea, loss of appetite, change in stool (chalky), chills, headache, myalgias -signs: jaundice and icterus due to deposition of bilirubin in skin and sclerae |
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What is the final clinical stage of hepatitis and what is the treatment for it, and in which types is it seen frequently?
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cirrhosis of liver
liver transplantation HBV, HBV/HDV, HCV |
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What is the leading indication for liver transplantation in the US?
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chronic hepatitis C infection leading to decompensated CIRRHOSIS of the liver
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What are some clinical manifestations of chronic liver disease and viral hepatitis?
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Due to hyperestrogenism:
-gynecomastia, testicular atrophy -spider angioma -palmar erythema Secondary to portal hypertension: -caput medusae, umbilical hernia -ascites, edema -hepatomegaly, splenomegaly -esophageal varices End stage: -Dupuytren's contractures Other: -jaundice and scleral icterus -muscle wasting -clubbing, white nail beds -hepatic encephalopathy |
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Describe the HAV pathogenesis.
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fecal to oral -> GI tract -> blood -> liver -> replicates in hepatocytes -> released via bile to intestines 7-10 days prior to clinical symptoms -> liver damage and symtoms result of immune response (T cell mediated) and not direct effect of virus
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What is significant about the HAV infection and the timing of clinical symptoms?
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Patients are infected a full week before the onset of clinical symptoms. Can transmit it without knowing (shedding virus in stool).
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What is tested for diagnosis of HAV and what do the positive results suggest?
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Detection of IgM antibody IgG shows up 1-3 weeks later. The IgG can be positive from prior infection or vaccination without having seen infection.
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What are some clinical features of HAV?
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-general hepatitis symptoms
-elevated serum aminotransferase levels, dark urine, light stool -adults usually more symptomatic -most cases resolve spontaneously in 2-4 weeks (some 3 months) -complete recovery 99% -no chronic form -lifelong immunity likely after infection or vaccination |
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What is clinically significant when comparing HAV to HEV?
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HEV has a high mortality in pregnant women
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How is chronicity set up in HBV?
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The dsDNA of the virus replicates to complete its circular DNA and then makes mRNAs (some translated into viral proteins). One of the mRNAs is replicated with a reverse transcriptase making the DNA that will be the core of the progeny virion and some of that DNA is also integrated in the host genome causing CARRIER state. Also the virus is very STABLE and RESISTS many stresses making it more infectious.
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What indicates low transmissibility in HBV?
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The HBV e Ab
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What conferes lifelong immunity to HBV?
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Detection of the HBsAb
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How are chronic carriers of HBV diagnosed and what percent of the of those infected does this occur?
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-Two positive HBsAg tests 6 months apart.
- 5% become chronic carriers |
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What are the HBV modes of tranmission?
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sexual
parenteral perinatal (all pregnant woman should be vaccinated if haven't yet) |
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What are some extrahepatic manifestations of HBV?
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glomerulonephritis
vasculitis arthritis rash angioneurotic edema (in ankles) |
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What are the chances of an acute HBV infection developing into a chronic HBV infection and what else can it lead to?
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-3-5% of adults and 95% of infants develop chronic HBV infection.
-chronic hepatitis -> CIRRHOSIS -> liver failure/HEPATOCELLULAR CARCINOMA -> liver transplant/death |
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What is significance of the WINDOW PERIOD during the course of a typical acute HBV infection?
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In the window period, if test for surface antigen and antibody, will get a false negative and miss the infection. Instead, the core antibody can be detected to tell if the patient is infected.
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What titers do you collect if you are suspicious your patient has an HBV infection?
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HBsAg and anti-HBc (surface antigen and core antibody)
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What titer would show an HBV immunity?
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anti-HBs (antibodies for the surface antigen)
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How do you diagnose HBV (chronic and acute)?
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-chronic: two positive HBsAg 6 months apart
-acute:- +IgM, +anti-HBc -HBV DNA usually positive for chronic and acute cases |
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What community has a high prevalence for chronic HBV?
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Asian American communities (10-25%, rest of US is <2%)
-leading cause of death in Asian American men in CA -50% of children born to mothers with chronic HBV in the US are Asian American |
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What is the treatment for HBV?
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-INTERFERON-ALPHA (pegylated and non-pegylated) parenteral administration
-LAMIVUDINE -mouth -ADEFOVIR DIPIVOXIL -mouth -Entecavir -Telbivudine -Tenofovir |
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What does HDV require for replication?
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-HDV is a defective virus that requires co-infection with HBV for replication
-HBsAg is its envelope (w/ ssRNA genome) |
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What antigens are encoded in HDV?
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only antigen encoded is the DELTA antigen
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What is the difference between HDV coinfection and superinfection wtih HBV?
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co-infection: infection with HBV at the same time as HDV - low risk of chronic infection
superinfection: infection with HDV in chronic HBV - high risk of chronic infection and severe chronic liver disease (fulminant liver failure) |
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What is significant about the Serologic Pattern of Chronic HCV?
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There is a fluctuating pattern of liver function measured by ALT. Also, there are still elevated levels of anti-HCV.
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How would you monitor chronic HCV?
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RNA levels - decide whether or not hte patient needs retroviral therapy and LIVER FUNCTION TESTS
-not useful to check for antibody b/c there are still elevated levels of anit-HCV |
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Which Hepatitis viruses can lead to hepatocellular carcinoma?
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HBV, HCV (as well as other chronic liver diseases and chronic alcoholism)
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How do you diagnose HCV?
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-HCV EIA or ELISA - assesses antibody; does not distinguish b/w acute and chronic
-HCV RIBA - antibody confirmation test; does not distinguish b/w acute and chronic -**HCV RNA PCR - detects viral RNA, not antibody -NAT (nucleic acid test) - detects HCV RNA |
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What test is necessary to confirm the HCV ongoing infection and what does it measure?
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HCV RNA PCR
-viral load (# of HCV/ml) -viral levels do not correlate with severity -viral levels do not correlate with response to treatment |
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How do you treat HCV?`
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pegylated interferon-alpha + ribavirin
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What is the number indication for liver transplantation?
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HCV
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