Upgrade to remove ads
Only $35.99/year

MICRO Exam 2: L31-32

Terms in this set (93)

Name the 5 RNA hepatitis viruses
Name the DNA hepatitis virus
A, C, D, E, G
B
Which viruses cause acute hepatitis?
Describe this type of infection.
A, B, C, D
sudden illness with a mild to severe course followed by complete resolution
Which of the following is not a characteristic of acute viral hepatitis?

A) Variable incubation period
B) 14-28 days later the patient develops jaundice
C) Flu-like symptoms
D) Necrosis of hepatocytes
E) All are characteristics of acute viral hepatitis
B) 14-28 days later the patient develops jaundice
• jaundice develops 1-2 weeks after infection
What enzymes are elevated during necrosis of heptocytes during acute viral hepatitis infection?
• aspartate aminotransferase (AST)
• alanine aminotransferase (ALT)
• gamma-glutamyl transpeptidase (GGT)
• alkaline phosphatase
Which viruses cause chronic viral hepatitis?
Describe the signs of infection.
B, C, D
• diagnosis difficult bc asymptomatic
• enlarged tender liver
• mildly elevated liver function enzyme levels
List the enzymes associated with the pattern of elevation seen in a hepatitis infection for each of the following.
• Hepatocytes
• Bile canaliculi
• Cell necrosis

• Initial phase
• Late phase
• hepato: AST and ALT
• bile: alkaline phosphatase and GGT
• necrosis: release of AST and ALT

• initial: high AST and ALT, low alkaline phosphatase and GGT
• late: swelling in liver, narrowing of bile canaliculi, backup of bilirubin in blood, elevated alkaline phosphatase and GGT
Describe the structure of HAV.
What family does it belong to?
How is it transmitted?
What type of hepatitis does it cause?
+ssRNA, naked icosahedral capsid
• picornaviridae
• fecal-oral route
• acute
Each year in the US, ________ cases of HAV are reported.
What causes this transmission?
6000
Poor hand washing, persons ingesting fecally contaminated drinking water, close person-to-contact in institutions such as a day care
(T/F): The HAV capsid is antigenic and the host produces anti-HAV IgG and later anti-HAV IgM.
False
• IgM then IgG later
Active HAV infection shows ____________ in the serum.
What indicates old infection, no active disease, and protective function?
anti-HAV IgM
anti-HAV IgG
Describe the treatment/prevention for HAV
• inactivated vaccine for high risk adults (travelers) and children
• once exposed, pooled immune serum globulin will prevent or decrease the severity of infection, if given early
Describe the structure of HBV
HepaDNAvirus
(HBV = Big and Bad)
• circular dsDNA
• enveloped iscosahedral capsid
• intact virus (Dane particle) = envelope + capsid with protein spikes
Describe how the HBV genome is unique
• some parts of it are double stranded and some single stranded
• positive strand (inner) is only 50-80% as long as the negative (outer) strand
Name the 4 proteins encoded by viral DNA in HBV
1. Capsid protein (capsid antigen) [HBcAg]
2. Envelope protein (surface antigen) [HBsAg] - anti-HBsAg are protective
3. Multifunctional reverse transcriptase/DNA polymerase
4. Nonstructural regulatory protein, X protein
Which anti-HBV antigen is protective?
HBsAg
What is the function of the X protein in HBV?
enhance DNA binding activity of other TFs
• associated with tumorigenic activity
HBV is unique because it replicates via ___________
RNA intermediate (Multifunctional reverse transcriptase/DNA polymerase)
How can HBV be transmitted?
• Blood: transfusions, needs, all body fluids
• Sex
• Birth: mothers with HBeAg have 90% transmission rate to offspring
Titer of HBV in acute infection is as high as _____ virus particles per ml.

What soluble component of the core is released and used as a marker for active disease and highly infectious state?
10^8

HBeAg
(T/F): HBV, HCV, and HDV can cause both acute and chronic viral hepatitis.
True
Describe the difference between acute, fulminant, and chronic HBV hepatitis
• acute: rapid onset, destruction of hepatocytes (elevated HBV Abs)
• fulminant: severe acute hepatitis with rapid destruction of the liver (1-2% extensive necrosis of liver in 1st 8 weeks, fatal in 8% of cases)
• chronic: asymptomatic carrier that never develops antibodies against HBsAg (anti-HBsAg)
Which type of chronic hepatitis is characterized by acute infection continuing without normal recovery (over 6-12 months)?

Which type of chronic hepatitis is described by low-grade "smoldering"?
chronic active

persistent (asymptomatic most of the time but have a higher risk of reactivation)
Chronic HBV has co-infection with _________ and can result in ____________ hepatitis
HDV, fulminant (severe acute)
In HBV infection, what causes liver injury?
Describe this mechanism.
cell-mediated immune response
• HLA-I cytotoxic T cells react specifically with HBcAg and HBeAg expressed on surface of infected hepatocytes
• immune complexes of Ab and HBsAg deposit in tissues and activate immune system
• results in arthritis, skin and kidney damage

• also enhanced NK cell activity along with production of IFN-alpha
Describe the timeline of acute HBV infection with complete resolution and immunity
• HBeAg ~6-14 weeks, anti-HBe after
• High HBsAg starting at 4 weeks, tapers at 24 weeks
• IgM anti-HBc develops at week 6, tapers at week 32
• Anti-HBs develops at week 32
• window period: gap at 24-32 weeks where HBV not detected in tests
In the timeline of infection, what would indicate a chronic HBV infection?
continued presence of HBsAg beyond 6 months and absence of anti-HBs
Describe the disease states associated with each of the following based on the serology of HBV.
• HBsAg
• Anti-HBsAg
• IgM anti-HBcAg
• IgG anti-HBcAg
• HBeAg
• anti-HBeAg
• HBsAg = DISEASE
• Anti-HBsAg = IMMUNE, CURE, No active disease
• IgM anti-HBcAg = New infection
• IgG anti-HBcAg = Old infection
• HBeAg = HIGH infectivity (active disease)
• anti-HBeAg = LOW infectivity
(T/F): Based on the serology of HBV, antibodies to HBcAg are not protective.
True
How is HBV treated?
• active immunization (against HBs - protective)
• passive immunizations: Hep B Ig, pooled from donors because they have high titers of HBs antibodies
• anti-viral agents (IFN-a, nucleoside analogs (lamivudine, adefovir, entacavir), combination therapy (nucleoside/tide analog and IFN))
What viruses is the leading cause of chronic hepatitis, where 1.5% Americans seropositive?

_____% of those with exposure and acute infection develop chronic hepatitis.
HCV ("non-A, non-B")

85%, 20% of those result in hepatocellular carcinoma
How is HCV transmitted?

What are the manifestations of infection?

How is HCV diagnosed?
parenterally, primarily via injection drug use

6-12 week incubation period
acute infection usually asymptomatic

test for anti HCV antibodies, detectable within 6-8 weeks after exposure (PCR)
• positive test confirmed by recombinant immunoblot assay (RIBA) or measuring HCV viral RNA
How is HCV treated?
• IFN and ribavarin: CHRONIC (pegylated IFN-1 + ribavarin not ideal)
• Teleprevir and Boceprevir: protease inhibitors (combo with pegylated IFN & ribvirin improved success rates 60-80% for HCV genotype 1)
Describe the structure of HDV.

How is it transmitted?
helical nucleocapsid (HBsAg), RNA

parenterally, can only replicate with help of HBV (co-infection) & cause ACUTE hepatitis
(T/F): Antibodies to HBsAg are only protective against HBV.
False
• protective against both HBV and HDV (only in the case of ACUTE hepatitis)
• if chronic, then no antibodies against HBs
• in chronic condition, anti-HDV are protective
How does superinfection of HDV occur?
HDV infects a person who has chronic HBV infection (like HBV carriers) resulting in acute hepatitis in a patient already chronically infected with HBV
What are the manifestations of HDV superinfection?

How is it diagnosed?
high incidence of acute FULMINANT hepatitis, cirrhosis, and greater mortality (5-15%)
• patients with chronic HBV cannot make anti-HBsAg so remain chronically infected with both HBV and HDV

• delta antigen and antibodies to delta antigen (anti-HDV Ab)
HEV is often referred a ______ hepatitis as it shares similarities with it.

How is HEV transmitted?

HEV is endemic to which parts of the world?
non-A

fecal-oral

Asia, India, Africa and Central America
HGV is a(n) (DNA/RNA) virus in the __________ family.

How is it transmitted?

How is this virus unique?
RNA, Flavivirus

transfusion, parenteral routes

not conclusively shown to cause liver disease
Which of the hepatitis viruses is a DNA virus?

A) HAV
B) HCV
C) HDV
D) HBV
E) HGV
D) HBV
Which of the following statement is true concerning hepatitis?

A) HAV has not been associated with chronicity
B) HBV can only establish pathogenicity in a symbiotic relationship with HDV
C) HCV is a rather indolent disease that rarely progresses to cirrhosis or Hepatocellular carcinoma
D) Hepatitis G virus is known to be the most aggressive pathogen of its class
E) The Dane particle is composed, at its core, of RNA and is self-limited
A) HAV has not been associated with chronicity
A 37-year-old man has been admitted with relatively early but definitively aggressive cirrhosis. He states that in his teenage years he experimented with IV drugs and admits to needing sharing. He has had a full course of interferon and ribavirin and is weak and thin. Despite this drug regimen, his disease has progressed. Viral studies and serology show this to be an RNA virus, genotype 1. You indicate he should be placed on the transplant list. Which of the following is the most likely etiology in this setting and with this data?

A) Hepatitis A
B) Epstein-Barr virus
C) Hepatitis C
D) Hepatitis B
E) Hepatitis E
C) Hepatitis C
After considerable lab testing and nucleic acid sequencing, you conclude your patient has a virus that contains RNA and can only replicate in conjunction with hepatitis B. This is most consistent with

A) Hepatitis A virus
B) Hepatitis B virus
C) Hepatitis C virus
D) Hepatitis D virus
E) Hepatitis G virus
D) Hepatitis D virus
Retroviridae are a large group of RNA viruses that infect animals and humans.

Describe the 3 big concepts - RETRO, GROW and BLOW.
Retro: contains RT (RNA -> DNA)

Grow: cancer, some carry oncogenes that cause malignant transformation

Blow: cytotoxic to certain cells, e.g. HIV
Malignant cells lose __________, divide continuously as long as there is nutrient supply.

___________ regulate the cell growth and stimulation of these causes intracellular phosphorylation of ________

Oncogenes like __________ oncogene encodes a transmembrane protein that also phosphorylates this AA but at 10 times the normal rate.
contact inhibition

growth factors (mitogens), tyrosine

Rous sarcoma virus (src)
Most of the retroviridae cause either _________ or _________

How do some retroviruses cause cancer directly (acute)? Indirectly?
leukemia, sarcoma

• direct: by integrating an intact oncogene into the host DNA
• indirect: activate host proto-oncogene
What is the difference between acute transforming and non-acute transforming viruses?
• acute: CARRY intact oncogenes within their viral genome, which when integrated into host DNA causes malignant transformation

• non-acute: do NOT carry oncogenes, activate host cell proto-oncogenes by integrating viral DNA into a key regulatory area
How does a proto-oncogene become activated to form an oncogene?
During normal viral infection and integration, a mistake in splicing occurs and a virus captures a proto-oncogene
AIDS is characterized by susceptibility to infection with opportunistic pathogens or occurrence of ___________ or ___ cell lymphoma and a profound (increase/decrease) in the number of CD___ T cells.
Kaposi's sarcoma, B

decrease, CD4
Which type of HIV is endemic in West Africa and India?

Which type is the cause of AIDS worldwide?
HIV-2

HIV-1
Describe the structure of HIV
• retrovirus
• 2 +ssRNA
• capsid
• envelope
There are 4 proteins in the capsid of HIV.

Which protein is used for early detection?
Which proteins are cleaved from p53 encoded by the gag gene?
p24
p17, p9, p7
The lipid membrane of HIV (acquired during budding from the host cell) contains two viral glycoproteins, _______and _______, cleaved from a common precursor _________
gp120 (bind), gp41 (fuse), gp160
The HIV virion contains what three virus specific proteins that are essential for replication?
• reverse transcriptase (RT)
• protease
• integrase
All retroviruses possess in their RNA genome, two ending _____ sequences, as well as ____, ____, and ____ genes.
long terminal repeat (LTR)
gag, pol, env
What are the functions of LTRs?
• Sticky ends: sequences recognized by integrase, involved in insertion into host DNA
• Promoter/enhancers: proteins bind to the LTRs that can modify viral DNA transcription
After the virus enters the body mainly via mucosal surfaces or injection into the bloodstream by contaminated needles, HIV enters cells by means of the two envelop proteins ________ and _______
gp120, gp41
What is the function of gp120 in initial HIV infection?

What is the function of gp41?
•120: BINDS to CD4 molecule on the cell surface (T cells, macrophages, microglia in the brain)

• 41: mediates FUSION of viral envelope with plasma membrane allowing viral genome to gain entry
In addition to CD4 molecule, what two cofactors are required for HIV entry into T cells and macrophages?
CXCR4 (fusin) and CCR5
After the virus enters the cell, RNA is transcribed into a single-stranded _______ by the enzyme ____________

Which enzyme degrades the RNA portion of the DNA-RNA hybrid?
complementary DNA (cDNA), viral reverse transcriptase (RT)

RNase H activity of RT
After RNase H activity degrades the RNA portion of the DNA-RNA hybrid, what is made and what is the template used for this?
double stranded cDNA using ss cDNA as the template
What inhibits the synthesis of cDNA by RT?
azidothymidine (zidovudine or AZT)
After a ds cDNA is made, it is integrated into the host genome by ____________ and replicates with the cell as a provirus
viral integrase
At least two surface receptors are required for attachment. CD4 by itself is not sufficient for HIV infectivity.

________ enhances the entry of T cell line-tropic HIV isolates
________ is specific for macrophage line-tropic HIV isolates
CXCR4 (fusin)
CCR5
CCR5 is a known receptor for all of the following beta chemokines except:

A) RANTES
B) MIP1-alpha
C) MIP-1beta
D) MIP1-delta
E) None of the above
D) MIP1-delta
HIV-resistant individuals are found to carry a mutant allele of _______
CCR5
What is seroconversion?
What is the window period?
Clinical latency?
infected person first exhibits detectable levels of anti-HIV antibodies in their blood serum
• window: time for Ab to develop
• latency: asymptomatic period, virus replicated in lymphoid tissue, CD4 T cells decline
In HIV infection, infected CD4 T cells are killed by _____ rather than by the virus itself.
Therefore, ___________ infections become frequent when the CD4 count falls below _______/μl.
cytotoxic T lymphocyte (CTL - CD8+), opportunistic, 500
How is the adaptive immune system affected by HIV infection?
• destruction of lymphoid follicles
• infected macrophages also spread the virus to other tissues, such as brain
• NK cells can kill HIV infected cells (infection of NK cells by HSV makes them susceptible to HIV)
• eventually, virus overcomes immune response and progresses to AIDS
Although natural killer cells have been shown to kill HIV infected cells, infection of these cells by which of the following makes them susceptible to HIV infection?

A) Respiratory syncytial virus (RSV)
B) Herpes simplex virus (HSV)
C) Hepatitis B virus (HBV)
D) Influenza virus (H1N1)
E) All of the above
B) Herpes simplex virus (HSV)
Compared to a healthy person with 1000 CD4+ T helper cells/μl of blood, HIV induced T cell death results in a decline of about _____ CD4+ T cells/μl a year.

A) 10
B) 30
C) 60
D) 100
E) 200
C) 60
What is the clinical significance of formation of multinucleated giant cells in HIV infection?
T-cell to T-cell fusion allows virus to pass from an infected to uninfected cell bypassing the blood
What is the result of B cell dysfunction with HIV infection?
Polyclonal activation of B cells results in outpouring of Ig causing hypergammaglobulinemia
What is the clinical significance of monocytes and macrophages in HIV infection?
reservoirs of HIV, migrate across BBB to brain
• results in HAND: HIV-associated neurodegenerative disease
What tests are most commonly used to detect HIV infection?

Which two tests detect the presence of antibodies against HIV?

Which test detects the presence of viral particles in the patient's blood or immune cells?
• Western blot
• Enzyme-linked immunosorbent assay (ELISA)
• PCR

Western blot and ELISA

PCR (p24 antigen)
What does it mean to be a long term non-progressor of HIV infection?
• infected with HIV but show no signs of disease progression for 12+ years
• disease progression halts for an extended period of time, but eventually progression to AIDS will occur
Describe Highly Exposed Persistently Seronegatives
• repeatedly exposed to HIV, but never become infected with HIV
• deletion of the CCR5 gene that inhibits the virus from entering their CD4+ T cells, thus inhibiting viral replication
Describe the issues related to HIV vaccines
• seq diversity (high mutation rate and recombination)
• infection of critical immune cells
• immune avoidance (masking of neuralization epitopes, viral mutation, counter-immunoregulatory mechanism)
• latency
• no ideal animal model to study immune system response
What is the mechanism of AZT (zidovudine or azidothymidine)?
blocks the reverse transcriptase from making the cDNA
What is the mechanism of non-nucleoside RT inhibitors (NNRTIs) like Viramune (nevirapine) and rescriptor?
stop HIV production by binding directly to RT and preventing cDNA synthesis
How do protease inhibitors work to treat HIV infection?
inhibit the viral protease that cleaves the Gag and Gag-Pol polypeptides and thus prevent viral maturation
List the modes of action of HAART drugs
1. Entry (fusion) inhibitors
2. Non-nucleoside RT inhibitors
3. Nucleoside/nucleotide analogues
4. Protease inhibitors
Describe the structure of Ebola virus

What diseases does the filovirus Ebola cause?

What is the fatality rate?
-ssRNA, non-segmented

Ebola hemorrhagic fever or Ebola virus disease (EVD)

70%
How is Ebola virus transmitted?

Onset of symptoms typically occurs ___ to ___ days (range = 2-21 days) after exposure to the virus.
• person-to-person direct contact of broken skin
• unprotected mucus membranes with body fluids (blood, feces, and vomit being the highest-risk fluids)
• also in semen, urine, breast milk

8 to 10
What is the 1st FDA-approved vaccine for prevention of EVD?

How is EVD treated?
Ervebo

• supportive care: fluid resuscitation, electrolyte correction, prevention and treatment of concomitant and superinfections, prevention of shock complications
• Ab therapy: Zmapp (combo of 3 monoclonal Abs)
• transfusion therapy
Describe the structure of SARS-CoV-2
+ssRNA
How is SARS-CoV-2 transmitted?

What is the incubation period?

What are the symptoms of COVID-19?
infectious respiratory droplets and person to person contact

2-14 days after exposure

fever/chills, cough, shortness of breath, fatigue, muscle/body aches, headache, new loss of taste/smell, sore throat, congestion/runny nose, nausea/vomiting, diarrhea
Entry of SARS-CoV-2 into cells mediated by viral spike protein that binds to human ____________ receptor and is proteolytically activated by human ___________
angiotensin-converting enzyme 2 (ACE2), proteases
Severe and critical cases of COVID-19 have high levels of ____________ leading to a ______________
proinflammatory cytokines, cytokine storm
How is COVID-19 treated?
• prevention: vaccination
• antiviral: Remdesivir (faster recovery for patients with COVID-19)
• Monocloncal Abs
• Corticosteroid dexamethasone (reduce mortality for ventilated pts)
• Convelescent plama (emergency use, hospitalized pts)
The envelope protein of HIV that mediates fusion of the viral envelope with the plasma membrane of the host cell is

A) gp41
B) p53
C) p24
D) gp120
E) p17
A) gp41
HIV-resistant individuals that are found to carry a mutant allele of CCR5

A) Respond better to HAART therapy
B) Inhibit CD8+ T cells from attacking the virus
C) Halts the disease progression for a period of time
D) Inhibit virus from entering macrophages and CD4+ T cells
E) Promotes rapid viral replication
D) Inhibit virus from entering macrophages and CD4+ T cells
Which of the following statements about AIDS therapy is correct?

A) Cytotoxic T lymphocytes can completely eliminate the virus
B) HAART therapy is the preferred monotherapy of choice
C) Monotherapy is more effective than combination therapy
D) Protease inhibits inhibit Nef genes
E) The most commonly used drug AZT is aimed at blocking reverse transcriptase from making the cDNA.
E) The most commonly used drug AZT is aimed at blocking reverse transcriptase from making the cDNA.
The viral protein that helps novel coronavirus (SARS-CoV-2) to enter into host cells is:

A) Neuraminidase
B) Hemaglutinnin
C) gp41
D) TMPRSS2
E) Spike protein
E) Spike protein
Sets found in the same folder