Viruses of Hematopoietic System Flashcards
Virus
Particles that can transmit genetic information from one cell to another, and from one organism to another
Why is a virus not really an organism?
It requires proteins that are made by the host cell.
–But it encodes it’s own proteins.
Viral Replication Requires?
- Gaining entry to host cell
- Replicating proteins
- Replicating nucleic acids
- Packaging proteins & nuclei acids into virions
- Exiting the cell.
Antiviral Therapy
-Inhibit viral genome replication by mimicking the shape of a nucleotide and ‘plug up’ the enzymes that replicate the viral genome
Requirement of antiviral therapies?
Drugs must have higher affinity for the viral enzyme than for the host enzyme.
Acycloivir
- Nucleoside analog
- viral thymidine kinase needed to phosphorylate prodrug –> active drug
Thymidine Kinase expressed when?
During S phase
aka virus can only replicate in proliferating cells.
BUT WAIT– virus has it’s own TK enzyme (classic is HSV)
–Cool, now we can make drugs that just disrupt viral TK :)
Viral Pathogeneisis:
Acute
Long term
Acute: cell death & inflammation
Long term: malignancies & immune suppression→opportunistic infections
Viruses oncogenes cause cancer in different spots:
- G1→ S phase checkpoint
- Regulation of cell death by apoptosis
- Immunological synapse (normal T cell activation)
Regulation of cell death by apoptosis
Bid/Bax complex=apoptotic (cytochrome C released into cytoplasm)
Bcl-2/Bid complex=antiapoptotic (doesn’t let cytochrome C release)
Regulation of cell death by apoptosis
Bid/Bax complex=apoptotic (cytochrome C released into cytoplasm)
Bcl-2/Bid complex=antiapoptotic (doesn’t let cytochrome C release)
–high ratio–>more likely to become malignant.
Cancer at Immunological Synapse:
Normal: T cell activated –> B cell proliferates –>secretes specific antibody
Epstein-Barr Virus= expresses homologs of host proteins that regulate B cell expansion–> Lymphoma :(
What components to viruses always have?
Protein and nucleic acid
Some have lipid envelope that is embedded with glycoproteins
Tropism?
What organism do they infect?
What cell types do they infect?
Role of thymidine kinase?
Regulate GTP production
-dsRNA, segmented NO envelope (tick is vector!) Icosahedral Tropism: pro-erythroblasts --> mature RBCs Saddleback fever pattern
Colorado Tick Fever Virus
Colorado Tick Fever Virus
Symptoms and tx
Saddleback fever pattern
-travel to mountains in West
Tx: supportive
Cytomegalovirus (CMV, HHV5)
Tropism:
Symptoms:
Tx:
Herpes virus (dsDNA, enveloped, icosahedral)
Tropism: Systemic. LATENT in CD34+ cells (monocyte–>macrophage)
Symptoms:
- – CMV infectious mononucleosis: Heterophile Ab negative, OWL’S EYES CELLS
- –congenital systemic CMV=deafness
Tx: supportive. Ganciclovir for immunocompromised pts
Herpes viruses characteristics
dsDNA
Enveloped
Icosahedral
CMV, HHV6&7, EVB, Kaposi sarcoma (HHV8)
Only non enveloped viruses
Colorado Tick Fever Virus
Parvovirus B19
HHV-6 & HHV-7 :exanthem subitum
Tropism:
Symptoms:
Tx:
–> ROSEOLA
Tropism: CD4+ T cells, (PBMNCs, epithelial)
Symptoms: rash after fever resolves
heterophile Ab negative mononucleosis
Tx: Supportive (anciclovir for immunocompromised pts)
HHV-6 & HHV-7 :exanthem subitum
Tropism:
Symptoms:
Tx:
–> ROSEOLA
Tropism: CD4+ T cells, (PBMNCs, epithelial)
Symptoms: rash after fever resolves
heterophile Ab negative mononucleosis
Tx: Supportive (anciclovir for immunocompromised pts)
Kaposi Sarcoma herpes virus (KSHV, HHV8)
Tropism:
Symptoms:
Tx:
Tropism: epithelial cells, B cells
Symptoms: in immunocompromised pts only: kaposi sarcoma, primary effusion lymphoma, multifocal Castlemans disease
tx: Ganciclovir, cidofir, foscarnet
Parvovirus B19
ssDNA
NON ENVELOPED
icosahedral
Tropism: erythroid progenitor cells
symptoms: erythema infectiosum: fiery red RASH on CHEEKS. Transient aplastic crisis with underlying anemia (think of cells it targets)
tx: supportive
Only virus with ssDNA?
Parvovirus B19
Human T lymphotrophi virus-1
HTLV-1
Retroviridae
ssRNA, positive
enveloped
icosahedral
Tropism: T cells (HTLV-1 mostly CD4+)
symptoms: Acute T cell lymphoma/leukemia (ATL): Viral transcription factor Tax drives proliferation; blocks apoptosis.
HAM/TSP: inflammation on the spine
Tx: chemotherapy/ BMT
Retroviridaes?
Human T Lymphotrophi virus 1
HIV
Ebola virus
Filoviridae
ssRNA, negative
enveloped
HELICAL/complex
Tropism: Macrophages
Sx: Hemorrhagic fever
Tx: supportive
ssRNA viruses
Human T lymphotrophi (ssRNA, positive)
HIV (ssRNA, positive)
Ebola(ssRNA, negative)
Viruses you treat:
Kasposi Sarcoma: ganciclovir, cidofir, foscarnet
HTVL-1: chemo/BMT
If immunocompromised, tx CMV and HHV6&7 with ganciclovir.
Kaposi’s encodes vCyclin, a protein with homology to human cyclin D, expect what?
increased transcription of E2F regulated genes.
Kaposi’s encodes vCyclin, a protein with homology to human cyclin D, expect what?
increased transcription of E2F regulated genes.
G1—>S checkpoint: what is going on?
- Cyclin D/ CDK4 activation
- Phosphorylates RB
- RB lets go of E2F
- E2F goes and makes a bunch of enzymes for cell replication and division.
