lecture 9 Flashcards
cytocidal effect of viruses on host cells
cell death via lysis or apoptosis
non-cytocidal effect of viruses on host cells
persistent infection
cell transformation effect of viruse on host cells
tumor cells
cytopathic/cytopathogenic effect
damage or morphological changes to host cells during virus invasion
cell fusion (syncytium of polykaryon formation)
- involves fusion of plasma membrane of four or more cells to produce enlarged cell with four or more nuclei, prone to mature cell death
- result from fusion of infected cell with neighboring infected or uninfected cells
inclusion bodies in host cell during viral infection
- abnormal structure in cell nucleus, cytoplasm, or both such as aggregates of proteins, have characteristic staining properties, associated with certain viral infections
- help to identify certain viral infection
characteristics of inclusion bodies
- accumulation of viral components
- result from degenerative changes in cell
- crystalline aggregates of virions
visible effects of inclusion bodies
- intracytoplasmic, intranuclear or both
- single or multiple
- large or small
- round or irregular
- eosinophilic/acidophilic or basophilic
- acidophilic- recognizes affinity for acid dyes such as eosin, appear pinkish
- basophilic staining- recognizes/affinity for basic dyes such as hematoxylin, purplish blue upon staining
mechanisms of virus-induced cell injury and death
- inhibition of host-cell nucleic acid synthesis
- inhibition of host-cell RNA transcription (mRNA production and processing)
- inhibition of host-cell protein synthesis
- some viruses cause lysosomes to release hydrolytic enzymes, then destroy host cell
- interference with cell membrane function
apoptosis
- process of programmed cell death, mechanism of cell suicide, host activates as last resort to eliminate viral factories before progeny virus production is complete
- different from lysis- viral replication is complete, host cell destroyed, new virions released
role of capsases in apoptosis
- activation of host-cell capsases mediates death of cell
- once activated, capsases responsible for degradation of cell’s DNA and proteins
intrinsic (mitochondrial) apoptotic pathway
-activated as result of increased permeability of mitochondrial membranes subsequent to cell injury
extrinsic (death receptor) pathway
-activated by enlargement of specific cell-membrane receptors which are members of TNF receptor family (TNF, Fas, others), thus binding of cytokine TNF to cell receptor can trigger apoptosis
cytotoxic T lymphocytes and NK cells
- can also initiate apoptosis of virus infected cells
- use perforin and granzymes, which activate capsases inside target cell
antibody-dependent cell mediated cytotoxicity
- resulting from surface membrane fusion of enveloped viruses
- viral glycoproteins are retained on cell surface, since these are antigenic, the cell can become a target of the immune system of the host
- antibody binds Ag on surface of target cell
- Fc receptors on NK cell recognize bound Ab
- cross linking of Fc receptors signal NK cell to kill target cell
- target cell dies by apoptosis
cell transformation
-changing of normal cell into cancer cell
neoplasia
-descriptive term that denotes abnormal tissue overgrowth that may be either localized or disseminated, it is the process that leads to the formation of neoplasms (carcinogenesis )
oncology
study of neoplasia and neoplasms
benign neoplasm
growth produced by abnormal cell proliferation that remains localized and does not invade adjacent tissue
malignant neoplasm (cancer)
locally invasive and may also be spread to other parts of the body (metastasis)
oncogenic viruses
-cause or give rise to tumors
metastasis
-spread of cancer cells from part of body where it started (primary site) to other parts of the body
proto-oncogenes
encode proteins that function in normal cell growth and differentiation
tumor suppression genes
- Rb and p53
- plays a role in keeping cell division in check, encodes proteins that regulates and inhibits uncontrolled growth
oncogenes
-mutated forms of proto-oncogenes or aberrantlye xpressed proto-oncogenes
retinoblast protein (Rb)
- important tumor suppressor gene/protein that blocks E2F and keeps cell division in check
- E2F facilitates cell division
p53 protein
- important tumor supressor gene/protein that prevents cells with damaged DNA from entering cell division
- tries to mediate repairing of damaged host cell DNA
- if damaged DNA cannot be repaired, p53 mediates apoptosis of cell with damaged DNA
tumor viruses/oncogenic viruses
- cause cancer
- oncogenic viruses generally have DNA genome, or generate DNA provirus after infection (retrovirus)
oncogenic DNA viruses
- have viral oncogenes in the viral DNA (oncogenes are natural part of viral DNA)
- oncogenes cause cancer in host cells, may also help in virus replication process
- when oncogenic DNA viruses infect permissive cells, they can replicate successfully (no cancer)
- when oncogenic DNA viruses infect non-permissive cells, they cannot replicated, viral DNA integrates into host DNA or may remain episomal (like plasmid) results in cancer
productive infection in permissive cell
- virus completes its replication cycle, resulting in cell lysis
- no cancer
non-productive infection in non-permissive cell
- virus transforms cell without completing its replication cycle
- cancer
- viral genome, or truncated version of it is integrated into cellular DNA, alternatively the complete genome persists as an autonomously replicating plasmid (episome)
actively transforming retrovirus
viruses steal proto-oncogene from infected host cell DNA, then converts proto-oncogene into oncogene
slow/chronic transforming retrovirus
- virus genome gets inserted into the regulatory (enhancer region) gene of host cell DNA
- as result of this insertion, regulatory gene cannot function properly
- no control on proto-oncogene of host DNA
- excessive cell division/cancer
tumor antigens
-new antigens appear on the surface of tumor cells that may provoke immune response
expression of tumor antigens
FOCMA
