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14 Cards in this Set
- Front
- Back
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What changes are observed in cancerous cells?
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-early notable changes are loss of contact inhibition, transformed cells no longer stop growing when they come in contact with other cells but pile up as they grow in 3D rather than just as a monolayer
*cancer may only result if immunological surveillance fails |
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What virus families are oncogenic? How do DNA and RNA viruses differ in their oncogenesis?
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-7 virus families:
•DNA viruses (5) - poxvirus, herpesvirus, adenovirus, papillomavirus, and hepadnavirus •RNA viruses (2) - retrovirus and flavivirus |
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What are oncogenes? proto-oncogenes? What are tumor suppressor genes?
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-oncogenes were originally identified in retroviruses and may be referred to as v-onc genes
-the term is now applied to any genetic element associated with induction of cancer -in normal uninfected cells there are corresponding genes termed c-onc genes or proto-oncogenes -these are critical in controlling growth, division, and differentiation of cells -these include functioning as growth factors, growth factor receptors, intracellular signal transducers, and nuclear transcription factors -tumor suppressor genes and growth cycle control proteins exert a negative effect on regulation of the cell cycle -regulate normal cell growth and differentiation by control of cell cycle, DNA repair, or apoptosis -infection of cells by viruses that interrupt the function of these proteins can lead to neoplastic transformation because the cell cycle may continue on unchecked and proteins important in effecting apoptosis may be non-functional |
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Which retroviruses cause cancer? What 3 main genes are in the genome of retrovirus? How do they replicate? What 2 types of retroviruses are there?
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-includes feline leukemia virus, bovine leukemia virus, avian leukosis viruses, porcine lymphosarcoma virus, murine leukemia virus, and dermal sarcoma virus in fish
-the genome of retroviruses contains 3 main genes: gag (coding for the core nucleocapsid structural protein), pol (coding for the reverse transcriptase) and env (coding for envelope proteins -in a typical infection, a DNA copy of the viral genome is formed and integrated/inserted into the cellular genome -in addition to the above gene elements, some retroviruses carry a v-onc gene, a DNA copy of which may become inserted into the cellular genome along with a DNA copy of the remainder of the viral genome 2 TYPES: ❤Endogenous retroviruses: -are integrated as a DNA provirus into the cellular genome and are replicated with each cycle of cell division along with the cell genome -virus may never be expressed but the viral genome is passed from generation to generation of the host in the germ line cells (vertical transmission) -they do not carry a v-onc gene and usually are not oncogenic but rarely may be associated with leukemia late in the life of the infected host ❤Exogenous retrovirus: -productively infect cells and are transmitted horizontally, behaving just like any other infecting virus -the oncogenic retroviruses are in this grouping and are further divided into replication competent and replication incompetent retroviruses |
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What is a replication incompetent retrovirus?
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❤REPLICATION INCOMPETENT
-carry an oncogene but it is at the expense of a complete copy of one of the other viral genes, usually the env gene -this means the virus cannot complete the full replication cycle, giving rise to progeny virions unless the cell that it infects is co-infected with another complete retrovirus -when this dual infection occurs the incomplete virus acquires an envelop courtesy of the complete virus, giving rise to an infectious, hybrid virus -such hybrid viruses are very efficient at causing cancer because they add an oncogene to the host's genome causing neoplastic transformation of the host cell -up to 100% of infected animals develop cancer after a short (few days) incubation period after infection |
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What are replication competent retroviruses?
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-most do not carry a viral oncogene but cause transformation of the infected host cell by inserting the DNA provirs in proximity to the c-onc gene and promoting its expression (possibly by viral promoter sequences)
-the insertion of the proviral genome close to the c-onc is essentially a chance event and numerous infection cycles may occur before the provirus is inserted in a position that causes transformation -there is a longer incubation period (weeks to months) and usually less than 100% of infected animals develop cancer |
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How is the Rous sarcoma virus of chickens unusual?
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-unusual as a replication competent retrovirus because it carries a full set of functional viral genes plus an oncogene
-it thus infects cells productively without the need for a helper co-infecting virus and, because it carries a v-onc, it rapidly causes neoplasia in a very high proportion of infected birds leading to death in as short a time as 2 weeks after infection |
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How do DNA viruses cause cancer?
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-DNA oncogenic viruses may undergo productive infecion in cells leading to lysis and death of the cell or undergo non-productive infection in which the cell is transformed but the virus does not complete its replication cycle
-in the non-productive infections the viral genome or part of it may be incorporated into the cell genome -alternatively the whole viral genome exists as an autonomously replicating plasmid -some DNA viruses such as polyomaviruses, papillomaviruses, and adenoviruses contain genes analogous to the oncogenes of retroviruses and which act by similar mechanisms |
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How do poxviruses cause cancer?
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-poxviruses replicate entirely in the cytoplasm of cells and there is no evidence that poxvirus DNA is ever integrated into cellular DNA
-there is an early viral protein expressed in poxvirus infected cells that has close homology with epidermal growth factor and the expression of this may be why some poxvirus infection are characterized by cellular proliferation -the cellular proliferation associated with poxvirus infections results in local benign tumor like lesions that are never malignant -infections with rabbit fibroma virus, squirrel fibroma virus and Yaba monkey tumor virus produce lesions of this type |
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How do papillomaviruses cause cancer?
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-papillomaviruses cause warts on the skin and mucous membranes of most species
-usually these proliferative outgrowths are benign and regress spontaneously -however, under the influence of co-factors, only of which some are known, the lesions progress to malignant growths e.g. many bovine papillomaviruses do not cause carcinomas, cattle with type 3 who eat bracken fern develop carcinomas of the intestinal tract & bladder e.g. viral papillomas around the eyes of cattle (particularly white-faced breeds such as Hereford) in northern Australia often transform to malignant carcinomas -it is believed that UV radiation is the necessary co-factor |
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How do hepadnaviruses cause cancer?
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-naturally occuring hepatic carcinomas in mammalian and avian hosts are associated with infection with these viruses
-examples include duck hepatitis virus and woodchuck virus -hepatitis B in humans is an example -in ducks the ingestion of mycotoxins in feed is a recognized co-factor leading to malignancy and in both animals and humans the chance of developing carcinomas is greatly increased if infection occurs at birth |
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How do herpesviruses cause cancer?
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-Marek's disease of chickens is caused by infection with a herpesvirus that contains retroviral v-onc genes
-the neoplasm involves T lymphocytes, which proliferate and invade many tissues including nerves -often Marek's disease is first identified when flocks shown neurological signs (torticollis & paralysis of wing or leg) -vaccines comprised of heterologous herpesviruses (such as turkey herpesvirus) and attenuated viruses are used to prevent tumour development and these vaccines do not contain the v-onc genes |
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Why is the oncogenesis of viruses not so simple?
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-often there is a need for co-factors and there is usually a multistep series of events
-for some viral neoplastic diseases there is variation in susceptibility to developing cancer in different genetic strains of the same host species -can use selective breeding to reduce losses due to cancer -oncogenic viruses may be regarded as carcinogens capable of initiating a chain of 2 or more events -they may act as a promoter or initiator -one view is that c-onc genes are targets for carcinogenesis, and that malignancy requires expression of more than one class of oncogenes as well as perhaps mutations of critical tumor suppressor genes |
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Can we prevent oncogenesis?
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-removal of the virus is often sufficient
-can be achieved by quarantine and hygiene methods to prevent exposure or by vaccination -e.g. we have a vaccine for Marek's disease in poultry e.g. childhood vaccine for hepatitis B to prevent hepatic cancer e.g. vaccine against human papillomavirus to prevent cervical cancer |
