Download Immunology Stack

HIV, Hepatitis, Herpes
Slackers Facts by Mike Ori
Disclaimer
The information represents my understanding only so errors and omissions are
probably rampant. It has not been vetted or reviewed by faculty. The source is our
class notes.
The document can mostly be used forward and backward. I tried to mark
questionable stuff with (?).
If you want it to look pretty, steal some crayons and go to town.
Finally…
If you’re a gunner, buck up and do your own work.
What are the retrovirus groups
Oncoretrovirus
Lentivirus
What are the members of each retroviral group?
Oncoretrovirus – HTLV I/II
Lentivirus – HIV I/II
Describe retrovirus morphology
Encapsulated icosahedral ssRNA (+) diploid
What do the name prefixes tell you?
Onco = tumor
Lenti = slow
What is the target tissue for retroviruses
T cells
What tumors are associated with HTLV
HTLV I – Adult T-cell leukemias
HTLV II – Hairy cell leukemias
What are the three most important retroviral
proteins?
Reverse transcriptase
Integrase
protease
Describe retroviral promoters
Consist of long terminal repeats that are
situated upstream of viral genes
What are the products of the gag gene
Structural genes for matrix, capsid, nucleocapsid
What is the function of the pol genes
DNA synthesis and maintenance and protein
activation.
Protease, reverse transcriptase, integrase
What is the function of the env genes
Surface glycoproteins and transmembrane
proteins
GP120 and GP41
What does HIV rev do?
Transports mRNA from the nucleus
What does HIV tat do
Promotes the transcription of HIV genes by
interacting with LTR.
What are the analogous HTLV genes for tat and
rev?
Tax and rex
What is the basis for HTLV oncogenesis?
Tax interacts with host cell promoter sequences
that induce oncogenesis.
Is HIV oncogenic
No, HIV tat protein is more specific and does not
interact with host cell promoters.
What the general mechanisms of oncogenesis
Expression of viral genes that interfere with or
cause over-expression of host proteins that
lead to defective cell cycle maintenance.
Insertional mutagenesis - Insertion of viral
genome into the host genome in a way that
causes dysregulation.
Acute transforming viruses – incorporate a host
oncogene in the viral genome.
What are the primary HIV surface glycoproteins
and what are their functions?
GP120 – interacts with host cell receptors
GP41 – initiates fusion of viral and host
membranes
What are CCR5 and CXCR4
These are coreceptor molecules on the surface
of some human cells whose binding is
required in addition to GP120-->CD4
Where are CCR5 and CXCR-4 found
CCR5 is found in dendritic cells and
macrophages in the periphery. CXCR-4 is
found on CD4 T-lymphocytes
Where is the highest concentration of HIV virus
found
In lymph nodes
Describe why antibodies are less effective
against HIV
HIV infects adjacent cells during the budding
process. It is not exposed to antibodies. Note
that HIV proteins on the plasma membrane
are targets for antibodies though.
How does HIV reduce its exposure to cytotoxic
T-cells
It down-regulates MHC-I and MHC-II
Which is more infective for sexual transmission
CCR5 or CXCR-4?
CCR5. It is found on dendritic cells and
macrophages
List the hepatitis viruses
A, B, C, D, E, G
Where is F?
List the routes of transmission for each
A,E – enteric
B,D – Sex, blood, and rock and roll
C – Blood
G – Enteric?
Which viruses are associated with hepatitis
EBV
CMV
VZV
Yellow fever
What family does hep A belong to?
Picornaviridae
How do people come into contact with HAV
Transmission is ultimately fecal oral
Person to person
Shellfish
Water
What are the words to the hepatitis song aired
on Phoenix TV in the late 70’s?
Hepatitis has some symptoms we should learn to recognize
Like fever, feeling very tired and loss of appetite.
Your stomach hurts, you feel real sick, you will not eat a bite.
Your eyes sometimes look yellow when they only should be white.
Wash your hands after going to the bathroom
Wash your hands after changing baby too
'Cause we don't want to spread hepatitis
And we don't want hepatitis to catch you. Who? YOU!
What is the diagnostic test for HAV
IgM titer
What is the incubation period for HAV?
14-40d
Describe the structure of hepatitis B
Smallest DNA virus. Partial double strand
circular genome. Enveloped virus
Why does Hep B have a reverse transcriptase
Hep B uses RT during the viral replication
process to convert whole genome RNA
transcripts into DNA.
Where does reverse transcription occur for hep
B?
In the nascent virus particle.
Why is the second strand often incomplete?
There are insufficient nucleotides enclosed in
the viral envelope to complete the strand
Why are RT inhibitors relatively ineffective
against HBV?
Penetration of the viral coat in sufficient
concentration is a barrier to their efficacy.
What is the epidemiology of HBV?
0.1 to 0.5% chronic carriers. 50% of infections
are related to sexual activity.
What % of infected people become chronic
carriers?
10-20%
What are the long term sequelae of chronic HBV
infection?
Cirrhosis
Hepatocellular carcinoma (200x increase)
What is the incubation period for HBV?
160 days
What antibodies may be elaborated in response
to HBV?
Anti core
Anti surface
Anti E
Which antibody is considered protective?
Anti surface (anti HBsAg)
Which Ab is the first to be produced
Anti core
Which Ab is next
Anti E
Which antibody is last to be produced
Anti surface
What is the basis for inoculating infants against
HBV at birth
The incubation period for HBV is very long.
Hence, an early inoculation can prevent HBV
infection from establishing even if the neonate
is infected during parturition.
For what other virus is post exposure
vaccination used?
Rabies virus
What is the tx for HBV?
IFN-alpha
What family does Hepatitis B virus belong to?
Hepadenaviridae
What family does hepatitis C belong to
Flaviviridae
What are the other members of flaviviridae?
Yellow fever, dengue, St Louis, west nile
What is the chronicity for HCV?
85%
What is the primary mode of transmission of
HCV?
Needle sharing
What are the sequelae to HCV?
Cirrhosis
Hepatocellular carcinoma
What is the structure of HCV?
Enveloped ssRNA (+)
What is unusual about the chronicity of HCV?
Chronic viruses need to have a method of
genome persistence. RNA viruses (HCV=RNA)
are generally considered too fragile to persist
within cells (replicate or die) but HCV is able
to do so through unknown mechanisms.
What accounts for the damage to liver
parenchyma?
The immune response is probably the major
culprit causing damage.
What is the tx for HCV?
IFN-alpha +/- ribavirin
What family does hepatitis D virus belong to?
It is unclassified
What is the epidemiology of HBV?
Pretty much the same as HBV. Sex and blood.
What is unique about the relationship of HBV
and HDV?
HDV requires HBV as HDV’s genome does not
encode surface antigen. Thus it is impossible
to be infected with HDV unless HBV infection
is present.
Describe the hepatitis that occurs with HBV/HDV
coninfection
Fulminant hepatitis. Often presents as an acute
exacerbation in a chronic HBV patient.
What is the diagnostic test for HDV?
Anti-Delta antigen antibody titer
Describe the difference between HAV and HEV
HEV is an unclassified virus similar to calcivirus
(ssRNA (+) icosahedral). It is typically only an
issue in pregnant women where it can cause
fulminant hepititis. Typically found on indian
subcontinent.
Why am I not describing Hepatitis G
Because while it is found in 2% of blood donors,
it is not yet linked to disease.
To which family do herpes viruses belong
Please that’s easy…
Herpesviridae
What is the morphology of herpesvirus
Large enveloped linear dsDNA icosahedral and
enveloped virus
List the herpes viruses
HSV-1
HSV-2
Varicella-zoster (VZV)
Cytomegalovirus
Epstein-barr
HHV-6
HHV-7
HHV-8
What are the general rules for HSV 1 and 2
HSV 1 is above the waist, HSV 2 is below. These
are loose rules though as cross infection is
known.
What is the tropic tissue for HSV 1/2
Skin where it causes ulcerating lesions
Why do people have recurring lesions with HSV
1/2
HSV invades the trigeminal (1) or sacral (2) nerve
ganglions. It periodically reactivates and then
flows down the axons to replicate in the
epithelial cells.
What are the theories for HSV reactivation
1. Stress and other factors cause the latent virus
to begin replicating in the ganglion. The
resulting virions are shed from the axon tip
and then begin replication in the epithelium.
2. A low level of virus production occurs
within ganglion cells and is release in a burst
from the axon. These then replicate in the
epithelium. (store and release)
What are the gene classes in HSV. What are
their functions?
Alpha – immediate early, regulatory
Beta – early, genome replication
Gamma – Late, structural
What is the role of the LAT1 gene in maintianing
HSV latency.
LAT1 transcripts are antisense to alpha-0. This
blocks the action of alpha-0.
Thus neither can live while the other survives.
Where does HSV assembly occur
In the nucleus
Where does HSV bud from
The nucleus into the ER
On what cellular membrane are HAV’s spikes
found?
The inner membrane of the ER.
How is HSV released from the cell
By exocytosis
What form a blindness does HSV cause
Keratoconjunctivitis leading to corneal
ulceration
What is the form of the HSV genome during
latency
It is a circular extrachomasomal element
Which drug is used for TX of HSV?
Acyclovir
Foscarnet if resistant
What is the time course for VZV initial infection
Incubation for 14 days
Recovery in 2 weeks
What is shingles
Reactivation of VZV in older patients.
Describe the VZV vaccine
Live attenuated
Describe CMV clinical disease
Normally no sx except in immunocompromised
where it can have sx of pneumonia.
Can cause mono.
Describe the cytology of CMV infection
Nuclear and cytoplasmic inclusion bodies with
owl’s eye appearance. Giant cell formation.
Describe congenital CMV sequelae
Blueberry muffin babies
Hearing loss, retardation, hepatosplenomegally
What is the most common EBV disease
Infectious mononucleosis
Distinguish EBV and CMV mono
EBV is mono-spot positive
CMV is mono-spot negative
What is the basis of the mono-spot test
EBV elicits heterophile antibodies against sheep
RBC.
What long term sequelae is EBV associated with
Burkitt’s lymphoma in africa and
nasopharyngeal carcinoma in asia
What disease is caused by HHV-6?
Roseola infantum
Many other agents cause as well
What disease is associated with HHV-8
Kaposi’s sarcoma