Kaposi's sarcoma pathophysiology: Difference between revisions
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:* A suppressor of the viral lytic phase of replication | :* A suppressor of the viral lytic phase of replication | ||
==Genetics== | ==Genetics== | ||
* The main gene involved in the pathogensis of Kaposi's sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1).<ref name="pmid23685018">{{cite journal| author=Cancian L, Hansen A, Boshoff C| title=Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming. | journal=Trends Cell Biol | year= 2013 | volume= 23 | issue= 9 | pages= 421-32 | pmid=23685018 | doi=10.1016/j.tcb.2013.04.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23685018 }} </ref> | * The main gene involved in the pathogensis of Kaposi's sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1).<ref name="pmid23685018">{{cite journal| author=Cancian L, Hansen A, Boshoff C| title=Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming. | journal=Trends Cell Biol | year= 2013 | volume= 23 | issue= 9 | pages= 421-32 | pmid=23685018 | doi=10.1016/j.tcb.2013.04.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23685018 }}</ref><ref name="W">LANA. Wikipedia (2015) https://en.wikipedia.org/wiki/LANA Accessed January, 19 2015</ref> | ||
* Other viral latent genes involved in the induction of malignant cellular proliferation include: | * Other viral latent genes involved in the induction of malignant cellular proliferation include: | ||
:* vcyclin gene | :* vcyclin gene | ||
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:* ORF K12 gene (kaposins gene)<ref name="pmid10738139">{{cite journal| author=Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ| title=Characterization of the human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12). | journal=J Clin Virol | year= 2000 | volume= 16 | issue= 3 | pages= 203-13 | pmid=10738139 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10738139 }} </ref> | :* ORF K12 gene (kaposins gene)<ref name="pmid10738139">{{cite journal| author=Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ| title=Characterization of the human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12). | journal=J Clin Virol | year= 2000 | volume= 16 | issue= 3 | pages= 203-13 | pmid=10738139 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10738139 }} </ref> | ||
:* KSHV miRNAs<ref name="pmid25341664">{{cite journal| author=Plaisance-Bonstaff K, Choi HS, Beals T, Krueger BJ, Boss IW, Gay LA et al.| title=KSHV miRNAs decrease expression of lytic genes in latently infected PEL and endothelial cells by targeting host transcription factors. | journal=Viruses | year= 2014 | volume= 6 | issue= 10 | pages= 4005-23 | pmid=25341664 | doi=10.3390/v6104005 | pmc=PMC4213575 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25341664 }} </ref> | :* KSHV miRNAs<ref name="pmid25341664">{{cite journal| author=Plaisance-Bonstaff K, Choi HS, Beals T, Krueger BJ, Boss IW, Gay LA et al.| title=KSHV miRNAs decrease expression of lytic genes in latently infected PEL and endothelial cells by targeting host transcription factors. | journal=Viruses | year= 2014 | volume= 6 | issue= 10 | pages= 4005-23 | pmid=25341664 | doi=10.3390/v6104005 | pmc=PMC4213575 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25341664 }} </ref> | ||
==Associated Conditions== | ==Associated Conditions== | ||
==Gross Pathology== | ==Gross Pathology== | ||
Revision as of 15:54, 19 January 2016
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Kaposi's sarcoma pathophysiology On the Web |
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Risk calculators and risk factors for Kaposi's sarcoma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Pathogenesis
- Kaposi's sarcoma arises from endothelial cells, which are epithelial cells that normally lines the interior surface of blood vessels and lymphatic vessels.
- Kaposi's sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV8), which is also known as Kaposi's sarcoma-associated herpes virus (KSHV).
- HHV8 is usually transmitted through both saliva and semen via close sexual contact.
- Another minor route of transmission for HHV8 is through organ transplantation.
- A state of immunosuppression facilitates the development of Kaposi's sarcoma among patients infected with virus.
- Kaposi's sarcoma is a widely disseminated malignancy that may involve the skin, oral cavity, gastrointestinal tract, and respiratory airways.
- Kaposi's sarcoma is characterised by abnormal proliferation of endothelial cells, neoangiogenesis, and inflammation.
- Cutaneous manifestations of Kaposi's sarcoma is due to:
- The high vascularity of the tumor which leads to leakage of RBC and haemosiderin into the surrounding tissue
- The inflammatory process which surrounds the tumor leads to a mild painful swelling of the area
- The oncogenesis of HHV8 infection is due to a number of human cellular genes that have been incorporated through molecular piracy into the viral DNA sequence.
- The genes acquired by HHV8 will augment the cellular proliferation pathways of infected cells through various mediators and DNA synthesis proteins such as:
- Complement-binding protein
- IL-6
- BCL-2
- Cyclin-D
- VEGF
- PDGF
- βFGF
- TGFβ
- Interferon regulatory factor
- Flice inhibitory protein (FLIP)
- Dihydrofolate reductase
- Thymidine kinase
- Thymidylate synthetase
- DNA polymerase
- The augmentation of such cellular proliferation pathways will protect the virus from the immune system and allow a continuous viral replication during the latency period.
- During the latent period, HHV8 will express a viral latency-associated nuclear antigen (LANA-1) that acts as transcriptional modulator.
- The functions of HHV8 viral latency-associated nuclear antigen (LANA-1) include:
- A tethering molecule that stabilize the viral DNA to the cellular chromosome
- An inhibitor of p53 tumor suppressor protein
- An inhibitor of retinoblastoma (Rb) tumor suppressor protein
- A suppressor of the viral lytic phase of replication
Genetics
- The main gene involved in the pathogensis of Kaposi's sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1).[1][2]
- Other viral latent genes involved in the induction of malignant cellular proliferation include:
Associated Conditions
Gross Pathology
Microscopic Pathology
Gallery
References
- ↑ Cancian L, Hansen A, Boshoff C (2013). "Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming". Trends Cell Biol. 23 (9): 421–32. doi:10.1016/j.tcb.2013.04.001. PMID 23685018.
- ↑ LANA. Wikipedia (2015) https://en.wikipedia.org/wiki/LANA Accessed January, 19 2015
- ↑ Grossmann C, Podgrabinska S, Skobe M, Ganem D (2006). "Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype". J Virol. 80 (14): 7179–85. doi:10.1128/JVI.01603-05. PMC 1489050. PMID 16809323.
- ↑ Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ (2000). "Characterization of the human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12)". J Clin Virol. 16 (3): 203–13. PMID 10738139.
- ↑ Plaisance-Bonstaff K, Choi HS, Beals T, Krueger BJ, Boss IW, Gay LA; et al. (2014). "KSHV miRNAs decrease expression of lytic genes in latently infected PEL and endothelial cells by targeting host transcription factors". Viruses. 6 (10): 4005–23. doi:10.3390/v6104005. PMC 4213575. PMID 25341664.