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60 Cards in this Set

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What Herpes Viruses are in the Alpha group and and what is their site of Latency?
HHV-1, HHV-2 and HHV-3 (VZV; chicken pox & shingles)
Sensory Ganglia; Neurons
What Herpes Viruses are in the Beta Group and what is their site of Latency?
HHV-5 (CMV), HHV-6 (Human Herpes 6), HHV-7 (Human Herpes 7)
CMV= Lymphocytes & Macs
HHV-6 & 7= T-Cells & Monocytes
What Herpes Viruses are in the Gamma Group and what is their site of Latency?
HHV-8 (Karposis), HHV-4 (Epstein Barr)
B-Cells
What is the first site of attachement for Herpes viruses?
Proteoglycans (heparin sulfate)
Where does the uncoating occur and what happens?
Occurs at the nuclear membrane and the genome is released into the nucleus
What remains in the cytoplasm after penetration?
Some tegument proteins and mRNA remain in the cytoplasm
What do the immediate (alpha) genes do?
Encode alpha proteins
DNA-binding proteins that regulate/turn on transcription of viral mRNA's
What to the Early (beta) genes do?
Encode beta genes
Inhibit expression of Alpha genes
Initiate viral DNA replication
Shut down HOST cell replication/trans/protein syn.
Initiate expression of late genes
MINOR Structural proteins
What do late (gamma) genes do?
Encode gamma proteins
MAJOR Structural proteins
How does Assembly and release occur?
Genome is replicated in the nucleus
Structural protein are brought in where assemble occurs
Virus bud from the Nuc. Mem. BUT loses its Primary envelope
Released from cell via exocytosis
What is Acyclovir and what is effective agasint and what is not and why?
Guanosin Analogue used for treatment of the Herpes virus
Effective against HSV and VZV but more active against HSV
NOT active against CMV b/c does not encode a TK enzyme
What phorphorylates Acyclovir?
1st phosphorylation is added by a VIRUS enzyme TK (kinase)
2nd and 3rd Phosphorylation is from cellular enzymes
How does Acyclovir work?
After being phosphorylated it competively inhibits dGTP for insertion into the Viral Genome
Which then causes DNA chain termination b/c of lack of 3' OH group
What point of activity during infection does Acyclovir work?
Only has activity against Productive infection NOT latent infection
How does resistance occur for Acyclovir via TK?
Loss of gene encoding TK; not much of problem clinically though b/c these viruses are less virulent
Mutation of VK that reduces its affintiy for Acyc.
How does resistance occur for Acyclovir another way?
Mutation of DNA Pol. that reduces its ability to bind ACYC. Triphosphate
They still retain there virulence and often occurs in pts. who are immunocoprimised who are on prolonged treatment
What does Ganciclovir do and what is its MOA?
Guanosine Analogue; Active treament for CMV
MOA is very similar to Acyclovir but can just be phosphorylated by an Enzyme of CMV (UL97)
How does resistance occur for Ganciclovir occur?
Point mutations in gene UL97, which causes the inability to phosphorylate the drug
Mutation in the CMV DNA Pol. which causes less affinty for the Drug
What is Cidofovir used for and how?
Cytidine Analogue, used for treatment of CMV but competes for dCTP incorporation into DNA
BUT also has activity IN VITRO against other viruses
How does HSV-1 infect?
Via contact with contaminated saliva
Remains localized in the oral
Enters neurons at site of infection & travels to Trigeminal Ganglion where it establishes latent infection
How does HSV-2 infect?
Sexually transmitted
Remains localized at the genital mucosa
Enters neurons at site of infection & travels to Sacral Ganglion where it establishes latent infection
How does VZV infect?
Transmitted via respiratory
Initial replication occurs in the LUNGS
Disseminated by Blood & lymph to RES (liver, spleen, nodes)
Secondary viremia
Laten infection in Sensory Neurons
What is Herpes Stromal Keratitis?
Autoimmune disease of the EYE triggered by HSV
Can progress to blindness
Maybe a result of MOLECULAR MIMICRY
What is Herpetic Whitlow?
Infection of the finger
Enters through breaks in the skin
Often associated with healthcare workers or a child that sucks their thumb
Whatis Eczema Herpeticum?
Children with Eczema whic makes it easier for HSV to spread to the skin
What is Encephalitis and what causes it?
Mainly caused by HSV-1
Symptoms include FLU like symptoms, confussion, seizures & coma
Can HSV-2 cause meningitis?
Yes, but rarely causes encephalitis
What causes Neonatal herpes?
Usually HSV-2, but could be HSV-1 if mother has it on her genitals and is then usually contracted during birth; but can occur through nursing
DOES NOT CROSS PLACENTA
What is Varicella Pneumonia?
A complication of VZV, more likely in adults
Can be fatal
What is expressed in Latent Herpes and what occurs?
LATs which encode miRNA
miRNA get spliced from LATs and this then inhibits Apoptosis
Why is there no immune response in latent herpes?
B/C eventhough there are viral transcripts present ther are NO viral proteins
T-Cells can not detect infected cells
How does reactivation occur with herpes simplex?
Occurs following some kind of stress
Viruses travels down neurons to inital site of infection
Host response clears viruses more quickly then intial
How is the CMV transmitted?
Contaminated Saliva
Blood Transfusions
Sexually
Organ Transplants
In Utero
At birth
Nursing
Where does the productive infection of CMV occur?
Fibroblasts, ductal epithelial cells (why you see it in so many fluids), macrophages
Where does the latent infection of CMV occur?
Monocyte, stromal cells of the bone marrow
What is characteristic of CMV Mononucleosis-Like infection?
Symptoms less severe then EBV-Mononucleosis
HETEROPHILE ANTIBODY NEGATIVE
What are characteristics in CMV Congenital Infection?
Leading cause of congenital infection, in newborns is called Cytomegalic Inclusion; hearing loss and mental retardation are the most common consequences
How does Cytomegalic Inclusion Disease Occur and what are the common sympotoms?
Mother is CMV+ and baby is seronegative and then exposed to mothers CMV infection
Can occur In Utero
Hearing loss and mental retardation
Maternal AB is protective
How is the congenital infection of CMV diagnosed?
By isolating the virus from the infants urine during the first week of life
Damage is done at this point
What are the common manifestations of Perinatal CMV and when get it be Dx after birth?
Pneumonia and hepatitis
Can NOT be picked up in urine until 3-4 weeks after birth
What are some important facts about HHV-6 & 7?
NOT associated much with clinical disease especially 7
Most people have Ab, often asympotomatic
Replicates in salivary glands and transmitted via saliva
Latently infects T-Cells and Monocytes
What is HHV-6 & 7 associated with?
Exanthema Subitum; Roseola, Sixth disease
Mainly HHV-6
What are the receptors for EBV and where is it expressed?
CR2 or CD21 are the receptors MHC II are co-receptors
Expressed on B cells or the Oro and Nasopharynx
What are the markers for a productive infection of EBV?
EA, VCA, MA, ZEBRA
How is ZEBRA associated with EBV?
Marker for productive infection
Activates Immediate Genes
Not expressed in latent
What is expressed in the latent form of EBV and where does it occur?
EBNAs, LP, LMP, and 2 EBER
Only see a couple of viral proteins (EBNA) so immune does not see infection
Occurs in Memory B Cells
What distinguishes EBV from CMV?
The production of Heterophile Antibodies
What will result if EBV activated B cells are not destroye/controlled by T cells?
A lymphoma or leukemia may result
Where is the latent virus of EBV and where is reactivation common?
Latently infected memory B cells and is commonly reactivated in tonsils and oropharynx
If you have had EBV mono can you get reactivated?
Yes you can but might be asymptomatic and then just shed the virus and spread it with out knowing
What is clinical complication of EBV mono?
Splenic rupture
Pt. needs to stop playing contact sports
How do you Dx EBV Mono?
Downey Cells; large atypical T cells
Heterophile Ab
What is strongly associated with Burkitts Lymphoma (EBV)?
EBNA-1 antigen and EBV DNA are associated with the tumors
What are the neoplastic cells called in Hodgkin Lymphoma and how many subtypes is EBV assoicated with in HL?
Reed-Sternberg cells
There are 5 subtypes and EBV is associated with 3
What class of People is associated with Nasopharyngeal carcinoma?
Asian origin and EBV DNA cells is associated with tumor cells
What type of infection is Hairy Oral Leukoplakia?
PRODUCTIVE INFECTION of epithelial cells in the mouth NOT a B Cell transformation or CANCER
Opportunistic in AIDS
How is acute infection Dx of EBV done?
By detection of IgM or VCA or VCA Antibody
NOT EBNA
Detection of what would indicate previous infection of EBV?
VCA and EBNA
During reactivation of EBV what would you see and not see?
See EBNA; NOT IgM (only present in Acute)
What disease is associated with HHV-8 or KSHV and organ is it associated with?
Kaposi Sarcoma and sequences have been assoiciated with abnormal tissue of the PROSTATE