Viruses Flashcards
What is the genomic organization of parvovirus B19?
- neg ssDNA
- linear
- small (5000) nucleotides
- non enveloped
What is the capsid symmetry of parvovirus B19?
Icosahedral
What is the only virus we must know whose capsid symmetry is not icosahedral?
Ebola virus - helical
What does parvovirus B19 target?
- The erythroid progenitor cell specifically the P antigen.
- only humans
- immune if no P antigen
How does parvovirus B19 gain access to the body?
Respiratory route
What does the NS1 viral protein do in parvovirus B19?
It induces erythroid apoptosis
What is the typical clinical presentation of fifth disease?
- Erythrema infectiosum: macular rash and arthralgia
- slapped cheek appearance
- no vaccine or antiviral
- transient aplastic crisis if there is a blood problem
- chronic anemia
- fetal loss
- give IV-IgG in immunocompromized Pxs
How is parvovirus B19 diagnosed?
- clinical presentation
- IgG (7th day and on)
- PCR
What is the genomic organization of Colorado tick fever virus?
- DsRNA
- linear
- no envelope
What two viruses we need to know are non enveloped?
- parvovirus B19
- Colorado tick fever virus
What does the Colorado tick fever virus target?
- erythroid progenitor cells
What does the Colorado tick fever virus use to replicate?
The negative strand of its RNA
What is the clinical presentation of Colorado tick fever virus?
- fever (biphasic)
- chills,
- body ache
- lethargy/malaise
How is Colorado tick fever virus diagnosed?
- IgM
- ## reverse transcriptase PCR from blood or CSF
What is the treatment for Colorado tick fever virus?
Supportive care
What are some complications with Colorado tick fever virus?
- meningitis and encephalitis
- get blood culture and CT
What is the genomic organization of the EB virus?
- dsDNA
- gamma-1 herpes virus
- enveloped
What is the infection of the EB virus?
- lytic in epithelial cells
- latent on B-cells
What malignancies occur in EB?
- Burkitt’s and Hogkin’s lymphoma
- anaplastic nasopharyngeal carcinoma
- lymphoma food granulomatosis
How does the EB virus access B cells?
- in the tonsillar regions by CD21 on Bcells
- contact with epithelial cells
What is the EB virus oncogene and what is it’s homologous?
- LMP1 a homologous of CD40 TNF subtype
- activates an epidermal growth factor
What is LMP2 and what virus is it associated with?
- homologous of BCL-2
- activates B-cell proliferation/Antiapoptotic
What is the essential oncogene for EBV for Bcell transformation and what does it do?
- EBAN3C
- effects G1–>S checkpoint
- down regulates p53 and possibly a apoptotic protein
What is the classical presentation of EBV?
- Classic triad of infectious mononucleosis
- ## fever (10-14days mild), sore throat (3-5days severe), swollen lymph nodes (cervical)
How do you diagnosis EBV?
- VCA-IgM first until 4-6 weeks
- VCA-IgG forever
- mono spot test, IgM antibodies by bcells
- Downey cells - atypical lymphocytes, dark deformed nucleus and dark rimmed cytoplasm
What is X-linked lymphoproliferative disease?
- EBV
- develop fatal lymphoproliferative disease after EBV infection
- most die from IM
What is the molecular basis for X-linked lymphoproliferative disease in EBV?
- SAP proteins
- mutations in XIAP
- ITK, MagT1, CD27
What is the genomic organization of CMV?
DsDNA
Enveloped
What is the tropism for CMV infection?
- systemic: epithelial, endothelial, smooth muscle, macrophages, neurons
- latent: p antigen CD34 myeloid progenitor cells
How does CMV gain entry into the body and cells?
- sex, transfusion, saliva, urine, transplant
- 2 membrane glycoproteins (gB and gH-gL dimer)
How does CMV evade the immune system?
- disrupts MHC-1 viral protein complex
- makes miRNA that stop production of MCH-1
What is the clinical presentation for CMV and what does it cause?
- CMV infectious mononucleosis
- microcephaly, seizures, deafness, jaundice
- purpuric lesions resembling a blueberry muffin
- mental retardation
- hepatoslenomegaly
- heterophil mononucleosis (fever, lethargy, abnormal lymphocytes)
How do you diagnosis CMV?
- owl’s eyes on a blood smear
- ELISA for pp65 within leukocytes
- pp65 is part of the necleocapsid
What is the treatment for CMV?
- supportive if not bad
- for severe systemic congenital CMV use ganciclovir
What is the genomic organization of human herpes virus 6 and 7?
- DsDNA
- betaherpesvirinae
- roseolovirus
- lipid envelope
What virus is called roseola?
HHV 6 & 7
What is the tropism for HHV 6 & 7?
- CFU-GEMM (hematopoietic stem cell) and all derivatives
- epithelial cells
How do HHV 6 and 7 differ?
6:
7: more narrow tropism, Helper T cells, and epithelial cells in salivary glands and cells of the lung and skin
What is the clinical presentation of HHV 6 & 7?
- roseola or sixth disease
- exanthem subitum
- infancy or early childhood
- not itchy, morbilliform rash on trunk after a high fever resolves
How is HHV 6/7 treated?
Perhaps ganciclovir and foscarnet
What does HHV 6/7 cause in adults and immunocompromized people?
Adults: mononucleosis
Immcom: encephalitis (ganciclovir, foscarnet, Cidofovir) against HHV 6
What is the genomic organization of Kaposi Sarcoma virus (HHV 8)?
DsDN
What does HHV 8 cause?
Kaposi Sarcoma in immunocompromized Pxs
What is the tropism of Kaposi sarcoma virus?
B cells
What are the four proteins that HHV 8 (Kaposi sarcoma virus) has?
- vFLIP: regulates apoptosis
- vBcl-2: regulates apoptosis (both stop apoptosis)
- vGPCR: regulates cell fate (growth and migration)
- vCyclin: regulates cell division and apoptosis(?)
What is the treatment for HHV 8?
Latent phase targeting for re infection
- ganciclovir: chain termination
- Cidofir: inhib viral DNA pol
- foscarnet: pyro phosphate mimic on vDNA pol
What is the genomic organization of Human T-cell Lymphotrophic virus (HTLV1 & 2)?
- positive ssRNA
- reverse transcriptase
- enveloped
What is the tropism for HTLV?
T-cells
What is HTLV2 associated with?
No pathogenesis, more common in warm places
How does HTLV enter and activate?
- bind gp46 through fusion
- integrates into host DNA
- tax induced transcription
- Rex induced translation
What gene does Tax up and downregulate?
NF kappa beta (bind also to CREB, CREM) UP
DLG and IKB (degrade) DOWN
How does altering gene transcription contribute to transformation?
- activate cellular promoters and cell signaling cascades (Jak/Stat, PI3kinase, JNK)
- upregulate gene expression (protein)
What two things does HTLV cause?
- acute T-cell lymphoma (leukemia)
- HTLV-1 associated myeolopathy (HAM)/ tropical spastic paraparesis (TSP)
What is the presentation of ATL?
- malaise
- night sweats
- fever
- cachexia
- adenopathy
What is the clinical presentation of HAM/TSP?
- tcells trafficked into areas of spinal cord leading to astrocytosis and inflammation –> demyelination
- gait disturbance
- stiffness and weakness in legs
- back aches
- weak bladder
- constipation
What is the genomic organization of HIV?
- positive ssRNA with RT
- retrovirus of lentivirus
- envelope
What two viruses that we need to know are retroviruses?
HTLV and HIV
What is the tropism of HIV?
- CD4+ T helper cells primarily
- macrophages
- DCs
What are the key target molecules of HIV?
- CD4
- CCR5
- CXCR4
How does HIV-2 differ from 1?
- lower transmissibility and less potential to progress to AIDS
- more in west Africa
What are the t helper cell amounts by disease?
- normal: 1200-1500 per cubic mm
- immunocompromized: below 500
- AIDS: below 200
What is the role of t helper cells?
- mediate inflammation
- recruit B cells and proliferation
- decide when to stop the immune response
How is HIV diagnosed?
ELISA comfirmed by a western blot
What is the genomic organization of Ebola Hemmorrhagic Virus?
- neg ssRNA group V
- enveloped
- helical capsid
What viruses are dsRNA?
- Colorado fever tick disease
What viruses are dsDNA?
- EBV
- CMV
- HHV 6 & 7
- HHV 8
What is the tropism of Ebola virus?
- monocytes (macrophages and DCs)
What is the clinical presentation of Ebola?
- fever, myalgia, malaise,
- maybe chills,
- confused with malaria or dengue
- flu like symptoms and bleeding
How is death from Ebola?
- severe organ dysfunction
- encephalitis
- Anuria
- seizures
What is parvovirus 19 infection called?
Fifths disease
