Lecture 4 + 5 Flashcards
How do DNA viruses transcribe mRNA (what does it use as a template)?
DNA viruses transcribe mRNA using the (-) strand of the DNA genome as a template.
What enzyme is typically responsible for transcribing mRNA in DNA viruses?
For most DNA viruses, the enzyme responsible for transcription is the host RNA polymerase II.
Where does mRNA transcription take place in infected cells for most DNA viruses?
mRNA transcription takes place in the nucleus of infected cells, where RNA polymerase II is located.
What is a notable exception regarding the location of replication and the enzyme responsible for transcription among DNA viruses?
Poxviruses replicate in the cytoplasm of infected cells and thus encode their own RNA polymerase, because they can not rely on host RNA polymerase II for transcription (because its not in the cytoplasm)
How are the genomes of most (+) stranded RNA viruses translated? What is an exception?
The genomes of most (+) stranded RNA viruses can be translated directly by cellular ribosomes.
Retroviruses are an important exception, as their genomes require reverse transcription to form DNA before translation.
How do (-) stranded RNA viruses and double-stranded RNA viruses express their genes?
mRNA must be transcribed from the genome in order to have gene expression.
This function is performed by RNA-dependent RNA polymerases
Do (+) stranded RNA viruses need to incorporate an RNA pol inside the virus particle?
No, because the first thing they make is an RNA dependent RNA polymerase which can transcribe mRNA from the genome in order to have gene expression.
Do (-) stranded RNA viruses need to incorporate an RNA pol inside the virus particle?
Yes
These viruses package a virus-encoded RNA-dependent RNA polymerase into the virus particle, ensuring its presence in the infected cell
What type of viruses are retroviruses, such as HIV?
How do they replicate?
Retroviruses, such as HIV, are (+) RNA viruses.
Retroviruses replicate through a DNA intermediate.
- The RNA genome is “reverse transcribed” by the viral enzyme Reverse Transcriptase into double-stranded DNA
- The double-stranded DNA integrates into the genome of the host cell.
- The integrated DNA or provirus serves as a template for the synthesis of viral mRNAs using host RNA polymerase II.
- Host RNA polymerase II also synthesizes genome length (+)RNAs using the provirus as a template
Why is reverse transcription unique to retroviruses?
Animal cells do not contain an enzyme that can perform reverse transcription.
What are the steps involved in retrovirus gene expression?
- Virus binds to a receptor on the surface of the host cell, leading to fusion.
- RNA contained within the viral capsid is reverse transcribed into double-stranded DNA by the enzyme reverse transcriptase.
- The double-stranded DNA is integrated into the host cell genome with the help of the enzyme integrase.
- The integrated DNA, known as a provirus, serves as a template for the synthesis of viral mRNAs using host RNA polymerase II.
What potential consequence can occur
due to the randomness of virus integration… i.e. retroviruses integrate into certain locations within the host cell genome?
If retroviruses integrate into critical regions of the host cell genome, such as tumor suppressor genes or regulatory regions, it can lead to disruptions in cellular functions and potentially contribute to the development of cancer.
Why do retroviruses want to take place in a partially disassembled capsid during this process?
Retroviruses prefer to carry out their replication process within a partially disassembled capsid to evade detection by cellular sensors.
Naked DNA in the cytoplasm can trigger potent antiviral responses, such as the production of interferons. By maintaining intermediates within the capsid, retroviruses can evade detection and avoid triggering these responses.
What are the two groups of double-stranded DNA viruses based on their replication location?
- Replication exclusively occurs in the nucleus, relatively dependent on cellular factors.
- Replication occurs in the cytoplasm for viruses like Poxviruses, which have evolved all necessary factors for replication and are largely independent of cellular machinery.
Where does replication occur for single-stranded DNA viruses?
Replication occurs in the nucleus for single-stranded DNA viruses. This process involves the formation of a double-stranded intermediate that serves as a template for the synthesis of single-stranded genomic DNA.
How can certain DNA viruses lead to cancer?
Certain DNA viruses, such as those causing cancer, have relatively small genomes and replicate in the nucleus, utilizing the host cell machinery. Most cells in the body are not actively dividing, so they typically do not maintain large pools of the machinery required for DNA replication. Additionally, deoxyribonucleotide triphosphates (dNTPs), essential for DNA synthesis, are expensive molecules for the cell to produce.
Consequently, cells often have limited availability of dNTPs. To facilitate their replication, these cancer-causing viruses induce host cells to enter the S phase of the cell cycle, where DNA synthesis occurs. By inducing cell division, these viruses ensure a supply of cellular machinery and dNTPs for their replication.
If the viral infection is incomplete or the virus is defective, some infected cells may survive and continue to proliferate, leading to transformation into cancer cells. These cancer cells can evade cell cycle checkpoints and continue growing uncontrollably, contributing to tumorigenesis.
Where do most RNA viruses (viruses with RNA genomes) replicate? What is an exception?
In the cytoplasm of infected cells.
Orthomyxoviruses, such as influenza viruses, are a notable exception as they replicate in the nucleus of infected cells.
What is the general process of gene expression and replication for (+) RNA viruses?
The genome of (+) RNA viruses can be directly translated, producing a polyprotein. One of the proteins synthesized is RNA-dependent RNA polymerase, which copies the (+) strand into a (-) strand, serving as a template for the production of more (+) strands.
How do Flaviviruses and Picornaviruses regulate protein production from their (+) RNA genomes?
Flaviviruses and Picornaviruses produce a single polyprotein from their (+) RNA genomes.
The entire genome gets translated and cleaved into smaller parts by viral proteases.
However, this process results in a 1:1:1:1… ratio of proteins, which can be inefficient as some proteins are produced in excess while others are produced in insufficient quantities.
How do other (+) RNA viruses regulate protein production differently than flavi- and picornaviruses?
Other (+) RNA viruses, such as Alphaviruses, initially translate only the first open reading frame of their genome, producing RNA-dependent RNA polymerase.
This enzyme initiates replication, producing a full-length (-) strand, which serves as a template for more (+) strands. Additionally, the (-) strand can serve as a template for subgenomic mRNAs, which are smaller molecules initiating internally and translating into different proteins.
Alphaviruses can efficiently regulate protein production by generating more of one subgenomic mRNA, thus ensuring a more balanced production of proteins. This regulation is controlled by the efficiency with which the RNA-dependent RNA polymerase sits in front of a particular reading frame.
What is the consequence of the translation process for Flaviviruses and Picornaviruses in terms of protein ratios, in contrast to alpha viruses?
Flaviviruses and Picornaviruses produce proteins in a 1:1:1:1… ratio, which can be inefficient as some proteins are produced in excess while others are produced in insufficient quantities. This imbalance results in a surplus of capsid proteins relative to other essential proteins.
In contrast, Alphaviruses can adjust protein production by generating more of one subgenomic mRNA, ensuring a more efficient utilization of cellular resources. Additionally, (+) strand viruses can synthesize RNA-dependent RNA polymerase without needing to bring it into the cell, which enhances their replication efficiency.
How do segmented (-) RNA viruses regulate gene expression and replication?
Segmented (-) RNA viruses, such as influenza virus, have their genomes divided into multiple segments.
Each segment generally encodes a single protein.
The viral RNA polymerase copies the (-) strand into a complementary (+) strand, which can serve as mRNA for translation.
Additionally, the RNA polymerase synthesizes another (+) strand that does not get translated but serves as a template for the production of more (-) strands, which ultimately get packaged into new virus particles.
How do non-segmented (-) RNA viruses regulate gene expression and replication?
Non-segmented (-) RNA viruses, such as Ebola virus, have a single piece of RNA for their genome. These viruses synthesize sub-genomic mRNAs for gene expression.
The viral RNA polymerase transcribes mRNAs from the (-) strand for different genes.
Additionally, the anti-genome complement of the genome is made to serve as a template for the production of more genomes.
What are ambisense RNA viruses?
Ambisense RNA viruses have a genomic RNA that contains both (-) and (+) polarities.
Ambisense RNA viruses are often very deadly and have segmented genomes, with one segment referred to as L (large) and the other as S (small). Both segments encode two open reading frames: one for L and one for Z.
