Viral Genomes

virus

infectious, obligate intracellular parasite consisting of a protein coat and nucleic acid genome; not cells → parasites that rely on the cell to replicate

can viruses self-replicate?

no

t/f: viruses can translate protieins

false

viral genomes must make ______ that can be ready by host ribosomes

mRNA

viral genomes must make mRNA that can be read by __________

host ribosomes

central dogma

DNA → mRNA → protein

DNA is transcribed to RNA via ___________

DNA-dependent RNA polymerase

• DNA is template

• RNA is product

DNA-dependent RNA polymerase

transcribes RNA from DNA template

in ssDNA, what most occur before making RNA via RNA polymerase?

must make double stranded DNA via (DNA-dependent DNA polymerase)

DNA-dependent DNA polymerase

makes double stranded DNA from ssDNA

2 types of virus genomes

1. RNA

2. DNA

what enzyme produces RNA from RNA?

RNA-dependent RNA polymerase

is mRNA always the + or - strand?

+

DNA of equivalent polarity is ____ strand

+

RNA and DNA complements of + strands are ____ strands

-

mRNA is translated to ________

protein

examples of viruses with dsDNA genomes?

• herpes

• HPV

• smallpox

• adenovirus

no plant viruses are known to have ________ genomes

dsDNA

why are dsDNA genomes “forever”?

they deposit their genome in a cell and the cell can’t recognize that the viral DNA is not its own

example of virus with gapped dsDNA genes

hep B

what enzyme do vviruses with gapped dsDNA genomes use?

reverse transcriptase

reverse transcriptase

go from DNA → RNA → DNA → mRNA

viruses with ssDNA genomes

• TT virus

• B19 parvovirus (fifth disease)

• Parvoviridae (canine parvovirus)

viruses with ssDNA genomes have to go through _____________ to generate dsDNA

DNA-dependent DNA polymerase

viruses with + RNA genomes

• SARS, MERS

• Hepatitis C, west nile virus

• Poliovirus

• Norovirus

• Rubella virus

• Majority of plant viruses

pro of + RNA genome

genome directly acts as mRNA so can easily start producing protein

viruses with - RNA genomes

• Influenza

• Measles, mumps

• Ebola

• Rabies

• Lassa virus

RNA-dependent RNA polymerase can operate ___________

bidirectionally

cells lack ____________, making this enzyme a good target for antiviral drugs

RNA-dependent RNA polymerase

virus with dsRNA genomes

rotavirus

viruses with dsRNA genomes require which enzyme?

 RNA-dependent RNA polymerase

example of virus with + RNA with DNA intermediate

human immunodeficiency virus (HIV)

pathway for viruses with +RNA with DNA intermediate

ssRNA → dsRNA → dsDNA → mRNA

viruses with + RNA with DNA intermediate are _______

retroviruses

retrovirus

• family of RNA viruses

• has reverse transcriptase (makes complementary DNA copy of viral RNA which is integrated into host cell’s DNA)

what determines how a virus replicates?

genome type

where does DNA-dependent DNA polymerase act to replicate DNA?

nucleus

5 steps of infectious cycle

1. attachment

2. entry/uncoating

3. genome replication & protein synthesis

4. assembly

5. release

what parts of infectious cycle might be targets for medications?

• make virus unable to attach

• target enzymes that the cell doesn’t have (ex. RdR)

• release step

genome type of influenza

(-) RNA

genome type of measles

(-) RNA

genome type of ebola

(-) RNA

genome type of rotavirus

dsRNA

genome type of HIV

• RNA w DNA intermediate

genome type of herpes

dsDNA

genome type of HPV

dsDNA

genome type of smallpox

dsDNA

genome type of hepatitis B

gapped dsDNA

genome type of parvovirus

ssDNA

genome type of SARS

(+) RNA

genome type of hepatitis C

(+) RNA

genome type of west nile virus

(+) RNA

genome type of norovirus

(+) RNA

cancer

a malignant tumor; a growth that is not encapsulated and that infiltrates into surrounding tissues, replacing normal with abnormal cells; it is spread by the lymphatic vessels to other parts of the body; death is caused by destruction of organs to a degree incompatible with their function, by extreme debility and anemia, or by hemorrhage.

virologists, lead by Rous claimed that _________caused cancer

viruses

epidemiologists argued that __________ caused cancer, though they couldn’t offer a mechanistic explanation

exogenous chemicals

Rous proved that viruses can contribute to _________

oncogenesis

3 conditions for a virus to transform a cell

1. cytopathic effects must be reduced or eliminated (cell can’t die)

2. viral replication must be reduced or eliminate

3. cell must continue to divide (become immortal)

transformation refers to cells in _______

culture

oncogenesis

development of cancer

viruses are a contributing factor in _______ of human cancers

~20%

does cancer benefit the virus?

no

• it is side effect

how did the rouse sarcoma virus cause chicken cancer?

The viral genomes from sarcomas are RECOMBINANTS

- piece of ALV genome replaced with host DNA

- not random chicken DNA

- Chicken DNA encoded an ONCOGENE

what type of genome was Rouse’s sarcoma virus?

(+) RNA with DNA intermediate

• retrovirus

proto-oncogenes

• normal cellular genes

• found in all cells

• involved in control of cell growth

• highly regulated

• ~60 known

• abbreviated c-ONC

v-ONC

abbreviation for altered gene copy carried by retroviruses

are viral oncogenes precise copies of host genes?

no

genes in transfomring retroviruses were either ________ forms or __________ forms of normal cellular genes that regulate cell growth

mutant / over-expressed

diff b/w transforming retroviruses and transforming DNA viruses

transforming retroviruses push cell to continue to grow & divide while transforming DNA viruses just don’t send stop signal

do tumor suppressor genes act as transforming retroviruses or transforming DNA viruses?

transforming DNA viruses

what happens if tumor suppressor genes such as Rb and p53 are not active?

tumors develop

stop/go decision in the cell cycle is determined by …

nutrient concentration & growth factors in media

if conditions are not right, the cell cycle _______

pauses

Rb regulates …

restriction point decision

viral proteins can interfere with _____ regulatory mechanisms

Rb

how do viral proteins interfere with Rb’s regulatory mechanisms?

• proteins such as SV40 LT and Adenovirus E1A dismantle Rb/E2f complex → increased synthesis of cellular & viral replication proteins

• HPV E7  ubiquitinates RB → degradation

role of Rb

tumor suppressor protein → controls cell cycle (inhibits it)

the entry into S phase is under the control of _____

p53

p53

• transcription factor that decides whether cell enters S phase

• recognizes DNA damage in cells and stops cell cycle for repair

• recognizes viral DNA intermediates as abnormal

• monitors DNA damage of unscheduled DNA synthesis

cell does not want to ____________ damaged genetic info

duplicate

what protein recognizes DNA intermediates as abnormal?

p53

most frequently mutated gene in human tumors

p53

p53 and Rb cooperate to induce _________

apoptosis

as p53 accumulates, what happens to the cell cycle?

it stops

how do viruses inactivate p53?

• sequester it

• ubiquinitation → degradation

all cases of cervical cancer are attributable to ______

HPV