Microbiology Flashcards
1
Q
What are the 3 classifications of herpesviruses?
A
- Based on genome arrangement and latency tropism
- Alphaherpesvirinae: neurotropic latency, aggressive lytic growth -> Herpes simplex virus (HSV)-1, HSV-2. Varicella-zoster virus (VZV)
- Betaherpesvirinae: lymphotropic for latency, more insidious -> Cytomegalovirus (CMV), Human herpes-virus-6 (HHV-6), HHV-7
- Gammaherpesvirinae: lymphotropic for latency, more insidious -> Epstein-Barr virus (EBV),** HHV-8 (Kaposi’s sarcoma-associated herpesvirus)**
2
Q
What are the structure, genome, and replication cycle of Herpesviruses?
A
- Structure: icosahedral capsid surrounded by lipid envelope with about 12 virus-encoded glycoproteins
- Genome: large, linear, dsDNA ca. 150-250 kb pairs
- Replication: genome replicated, viruses assembled in the nucleus
- Self-limiting infections in which primary infection is often asymptomatic -> BUT, life-threatening infections or cancers can occur, especially in immune compromised hosts
2
Q
What is Crimean-Congo Hemorrhagic Fever Virus?
A
- Transmitted by ticks in Middle East, Africa & Europe
- Clinical disease rare, but severe in infected humans, with a 30% mortality rate
- Targets liver and vascular endothelium
- Symptoms include: headache, pain in limbs, and often bleeding from many orifices
3
Q
What is the epidemiology of EBV?
A
- Poor: infection at early age; Rich: adolescence or early adulthood -> both can lead to infectious mononucleosis
- 90 to 95% adult population contains antibody to EBV
- Can cause oral hairy leukoplakia in immuno-compromised hosts
- Posttransplant lymphoproliferative disease (PTLD) in some transplant patients
- Associated w/Burkitt’s lymphoma, nasopharyngeal carcinoma
3
Q
What other two diseases might EBV be linked to?
A
Hodgkin’s lymphoma
Multiple sclerosis
4
Q
What is the epidemiology of CMV?
A
- CMV is not highly contagious
- Infection by socioeconomic class:
1. Low: infection 1-2 y/o, up to 80% adults CMV+
2. High: infection 16+ y/o, about 50% adults CMV+ - CMV in: saliva, urine, breast milk, semen, cervical secretions, blood, (transplanted organs)
- At risk populations: neonates, day care workers, gay men, pregnant workers, immunocompromised patients
5
Q
What are the epidemiology and expressions of classical and US KS?
A
- Classical: Mediterranean pop and sub-Saharan Africa; NOT sexually transmitted in these cases
- US: most KS pts are AIDS pts; sexually-transmitted, but virus absent from semen and vaginal secretions
- Virus in saliva; how sexually transmitted not known -> typically, 10 year incubation period before KS
- May be relatively mild, but if pt severely compromised, can be life-threatening -> AIDS and non-AIDS forms, 95% of infections are asymptomatic
- Must have immune system loss for disease symptoms (old age in classical forms, and AIDS in gay populations)
- When symptomatic, tx in AIDS pts is tumor-specific (resection, chemotherapy) or targets HIV, but not HHV-8
5
Q
What are the symptoms and diagnosis of yellow fever? Prevention?
A
- SYMPTOMS: “flu-like” malaise progressing to severe hemorrhagic fever, hemorrhage of stomach lining often results in “Black Vomit”
- Progressive liver involvement results in marked jaundice with increasing levels of serum transaminases owing to direct viral-mediated liver damage.
- Once hepatorenal disease progresses, mortality rate can be 20%-50% w/death 7-10 dd after symptom onset
- DIAGNOSIS** **via any 1 of the following: virus isolation (i.e. incubating blood sample with cell lines to observe CPE), serologic identification -> ELISA for IgG or IgM, detection of viral genomic sequences by RT-PCR
- Fortunately there is an effective and safe attenuated, live vaccine
7
Q
How does CMV affect immunocompromised hosts?
A
- Especially at risk
- Most organ transplant pts get CMV, with pneumonitis representing the most life-threatening aspect
- Can result from infection by CMV+ donor or by reactivation of CMV+ recipient
- Prophylactic tx w/CMV Ig and ganciclovir looks promising in limiting complications
- When you think transplant patient, think CMV!
- AIDS pts prone to CMV retinitis, colitis, pneumonitis
7
Q
Why do we think HHV-8 linked to Kaposi’s sarcoma? What is KS?
A
- Evidence indicates HHV-8 is necessary, but not sufficient to cause Kaposi’s sarcoma (KS)
1. DNA sequences can be recovered from >95% of AIDS and non-AIDS KS tumors
2. >80% seropositivity among KS patients, - B-cell and endothelial latency tropism: KS tumors occur in lining of lymphatic system -> channels fill with blood cells, hence bluish, bruised lesions
7
Q
What is Hemorrhagic Fever with Renal Syndrome?
A
- Caused by Hantavirus, and found primarily in Europe and Asia
- Human infection from exposure to aerosolized urine, droppings, or saliva of infected rodents, or after exposure to dust from their nests
- Symptoms usually devo 1 to 2 weeks after exposure:
1. Liver and vascular endothelium targeted
2. Symptoms include: fever, hemorrhage, acute renal failure - Over **15% mortality rate **
8
Q
Describe the replication cycle of Faviviridae.
A
- Entry via rec-mediated endocytosis; nucleocapsid into cytoplasm after pH-dependent fusion event
- Genomic RNA 5’-cap (like host mRNAs) and translated by host ribosomes to generate single polyprotein, that is cleaved by combo of viral (cis-cleavage) and host (trans-cleavage) proteases
- Cleavage of polyprotein generates viral RNA- depend RNA polymerase which replicates the genomic RNA
- Structural proteins (capsid, envelope gps), also derived from polyprotein, assemble genomic RNA into virions that “bud” into ER or Golgi; enveloped viruses released from cells following transport to the cell surface
8
Q
What is classical Dengue Fever?
A
- Self-limited infection begins abruptly after 2-7 day incubation period w/high fever, headache, retrobulbar pain, lumbosacral aching, conjuctival congestion, and facial flushing
- Mottled rash may appear on day 1 or 2 and often pts complain of a metallic taste in their mouths
- Fever may be sustained for up to 6-7 days, but usually abates with cessation of viremia
- Initial symptoms followed by generalized myalgia with increasing severity of muscle and joint pain -> called “bonebreak fever” due to severity of the bone pain
- Characteristic finding: thrombocytopenia (< 100x109/L)
- Recovery complete but slow, w/fatigue, exhaustion often persisting for 2 weeks
8
Q
What are the 4 minimum WHO criteria for diagnosis of DHF?
A
- Fever
- Hemorrhagic manifestations (e.g., hemoconcentration, thrombocytopenia, positive tourniquet test)
- Circulatory failure (e.g. hypoproteinemia, effusions)
- Hepatomegaly
9
Q
What are the target organs and disease course of Flaviviridae?
A
- Initially replicate at site of inoculation (endo/epi cells around bite site) and establish transient primary viremia
-
3-7 days post-exposure, replicates in macros, spleen, or lymph nodes:
1. Results in a mild systemic disease
2. Most infections dont progress beyond this point - If infection not controlled by immune response, then secondary viremia ensues
- Secondary viremia results in severe systemic disease (e.g. hemorrhagic fever/shock syndrome).
10
Q
What are Bunyaviridae?
A
- Enveloped, spherical particles w/segmented, single-strand, negative-sense RNA genomes
- 300 different species grouped into five genera:
1. Rift Valley fever virus: mosquitoes (Africa)
2. Crimean-Congo virus: ticks (Africa, Middle East)
3. Hemorrhagic fever with renal syndrome (HFRS) virus (Hantavirus): rodents (Asia & Europe)
14
Q
Describe the Herpesvirus replication cycle.
A
- Undergo lytic replication in variety of cell types to propagate virus
- After attachment, penetration via virus gp-mediated fusion of envelope and PM -> released nucleocapsid migrates to nuclear envelope via microtubules, uncoats, and DNA enters nucleus, and virion components shut off host macromolecular syn
- Programmed expression of viral genes- cascade regulation
- Immediate early (IE) genes: virus-specific TF’s; use host RNA polymerase II, stimulate transcription at virus early promoters
- Early genes: encode nonstructural proteins, enzymes, DNA replication machinery, incl viral DNA polymerase, thymidine kinase (tk) which phosphorylates a variety of nucleotides besides thymidine
- Late genes: also dependent on IE TF’s plus genome replication for expression; encode structural proteins (capsids, glycoproteins); viral gps incorporated into virus envelopes and transported to cell surface where they can cause syncytia formation
- Virus assembly in nucleus, where nucleocapsids bud into perinuclear space -> migrate to cell surface and are released
16
Q
How is EBV linked to Burkitt’s lymphoma?
A
- Burkitt’s is a neoplasm of B-cells that affects bones of the jaw, and is endemic in central Africa, New Guinea
- Associated with three factors:
- Early EBV infection leading to latency
- Activation of c-myc
- Malaria
- Early detection allows cure rate of 80%
- Outside of Africa, only 20% of BL patients have EBV genomes in tumor
17
Q
What is the treatment for EBV?
A
- Supportive for mono; withhold athletes due to possible inflammation of spleen
- Treatment of oral leukoplakia is with acyclovir
