Lecture 6: Biological agents as causes of disease Flashcards
___ are the ultimate pathogen
viruses
viruses consist of
a simple genome encapsulated in coat protein - called a capsid. This may be enveloped in a membrane.
DNA virus life cycle
- entry
- uncoating
- transcription and translation
- genome replication
- assembly
- exit
Most viruses rely entirely on the ____ cellular machinery to make new viruses.
HOST
Viruses often shut down most cellular processes that are unrelated to their replication: inhibitory factors stop host-cell DNA, RNA, and protein synthesis.
some viruses integrate as __
DNA into the host genome for a period of quiescence or latency.
Viruses edit the cell either when
it lyses (dies) or by budding in the case of enveloped viruses
viruses are classed by their
genome type and how their mRNA (+ strand ) is made
Virus 1
DNA virus, RNA & DNA strand. (+&-) –> mRNA
Most similar to normal cells
Adenoviruses:respiratory disease, conjunctivitis
SV40 (simian virus 40)
Herpes viruses: chicken pox, herpes sores, carcinomas
Papilloma viruses: genital warts, cervical cancer
Virus 2
DNA virus, DNA or RNA –> DNA & RNA –> mRNA.
virus 3
RNA virus, DNA & RNA (+&-) –> mRNA
Segmented genomes (several pieces) Rotavirus: acute gastroenteritis
virus 4:
RNA virus, RNA (+) –> DNA (-) –> mRNA
mRNA makes polyproteins that are cleaved
Polio viruses, Toga viruses: yellow fever,
SARS viruses
virus 5:
RNA virus. DNA (-) –> mRNA
V The virion carries RNA transcriptase
“RNA-dependent RNA polymerase”
Ebola viruses, Influenza viruses
Paramyxoviruses: measles
virus 6:
RNA virus, RNA (+)
–> DNA (-) –> double stranded (=&-) –> mRNA (+)
VI Retroviruses - enveloped - reverse transcriptase
human T-cell lymphotrophic viruses: leukemia
human immunodeficiency virus: AIDS
virus 7
VII Double stranded DNA and Reverse transcriptase
DNA is made into genomic RNA
Hepatitis B Virus
Viruses have different entry strategies:
Like bacteria, viruses rely on receptors present on the host’s surface to gain entry into the cell. Check points at each step ensure that the next phase of entry is not entered prematurely
(4 different types)
DNA viruses: Papillomaviruses virus causes
6% of al human cancer in the world. Pap smear allows early detection and curative treatment
DNA viruses: Papillomaviruses virus results in malignant tumour how?
Proteins produced by the viral genome upregulate DNA replication and proliferation by the host cell to allow more production of viral genome.
Accidental integration of the virus can result in too much proliferation and is the first step in malignant tumour formation.
DNA viruses: Papillomaviruses virus genome contains several __
oncogenes
human genome is
3 billion bp
E6 & E7 in human genome normally act by
turning up the hosts DNA replication machinery - to make more virus, not necessarily more host cells.
Transformation results when the viral genome is integrated into the hosts genome and malfunctions producing too much E6 and E7. This results in unregulated cell proliferation.
DNA viruses: E6 and E7 take the brakes off
of host cel proliferation
E6 & E7 bind to..
the host proteins Rb and p53 to inactivate them. This release constraints on DNA replication. Mis-regulation of Rb and p53 is often involved with other viral as well as non-viral cancers.
retroviruses cause cancer by
incorporating human genes into their genome
oncogene:
a gene which in certain circumstances can transform a cell into a tumour cel
Retroviruses usually cause cancer by incorporating human..
proto-oncogenes into their genome. This is thought to occur when mistakes are made during integration of the viral genome into the host genome.
The genes are usually altered when incorporated into the viral genome. They referred to by a v- prefix:
v-abl (viral)
c-abl (host gene also called proto-oncogenes)
proof of retroviruses incorporating human genes:
Inoculation of 150 mice with MuLV results in one with a tumour. When MuLV is isolated from this mouse it has changed to Ab-MuLV.
porto-oncogenes are proteins involved with
cell proliferation
Most retroviruses that cause tumours have
oncogenes.
Many viral oncogenes are also involved with
non-viral cancers
c-src is a kinase that is powerful activator of
cell proliferation. Normally the cell down regulates c-src activity by phosphorylating one end of the protein (puts the brakes on). This causes the protein to fold on itself to become inactive
v-src does not have the
c-terminus - this change creates the oncogenic form of src.
Many oncogenes encode
host kinases which have lost regulation by fusion to viral genes or deletion of regulator sequences.
