TOPIC M: GENETICS OF VIRUSES Flashcards
What is the structure of the genome of viruses?
A virus is either a RNA or DNA virus.
For viruses with RNA genome,
-they may possess either POSITIVE sense RNA or NEGATIVE sense RNA.
- The genome is usually organised as a linear or circular molecule of nucleic acid, depending on the type of virus.
- In some viruses, the nucleic acid is single stranded, but in others it is double stranded.
- Some kinds of viruses may have more than one copy of the genome.
- Viral genomes also vary considerably in size, ranging from a few thousand to more than a hundred thousand nucleotides in length.
+ve sense: = to viral mRNA
-ve sense: complementary to viral mRNA
What is the structure of the capsid in a virus?
A protein coat enclosing the viral genome
Built from capsomeres, can carry viral enzyme molecules
Most complex capsids are bacteriophages, which have elongated icosahedral heads enclosing their genome.
Attached to the head is a tail sheath with fibres that the phages use to attach to a bacterial cell wall.
They serve to protect the viral genome.
What is the structure and function of the viral envelope?
Viral envelope encloses the capsids of many viruses which infect animals.
Comprises of hostcell ppl from the CSM, embedded with virally encoded spike glycoproteins.
VE protects the virion from enzymes and other chemicals, giving then an adv over capsid-only virions
Glycoproteins on viral env help viruses enter HC by recognising and binding to receptor molecules on specific host cells.
This host specificity results from the evolution of recognition systems by the virus, a lock-and-key fit between glycoproteins on the surface of the virus and specific receptor molecules on the surface of host cells.
What is the lytic cycle?
A phage reproductive cycle that culminates in the death of the host cell. T4 Phage is a virulent phage and only reproduces by the lytic cycle.
What are the main steps of the lytic cycle?
using T4 phage as an example (AESAR)
Attachment: T4 phage uses its tail fibres binds to specific receptor sites on the outer surface of an E.coli
Entry: Sheath of the tail contracts, injecting the phage DNA into the cell and leaving empty capsid outside.
Synthesis: Phage DNA directs synthesis of phage proteins and replication of phage DNA by host cell machinery. One gene expresesses codes for an enzyme that degrades host cell DNA. Phage DNA protected from degradation as it contains a modified cytosine that enzyme does not recog.
Assembly: Phage components are assembled with the help of non-capsid proteins to form new phages. Phage DNA is packaged inside the capsid.
Release: Phage directs production of an enzyme called lysozyme that damages the bacterial cell wall, allowing fluid to enter. HC swells and lyses, releasing new phages.
What is the lysogenic cycle?
lambda phage eg.
Temperate phages are capable of using two modes of reproduction within a bacterium. Lysogenic cycle allows of replication of the phage genome without destroying the host.
Describe the lysogenic cycle.
Lambda phage
- Attachment- phage uses tail fibres to bind to specific receptor sites on outer surface of E.coli.
- Entry- Phage uses specific pores in the cell surface of E.coli to inject DNA into the cell. Phage DNA molecule circularises within the host cell.
- Integration- Phage carries a gene that encode an enzyme [INTEGRASE], expressed soon after entry. Cuts host chromosomal DNA and inserts phage DNA into host DNA. Phage DNA in a bacterium is a prophage. Prophage gene could code for a protein that prevents transcription of the other prophage genes, genome remains dormant within the bacterium.
Everytime the E.coli cell prepares to divide it replicates the phage DNA, passing the copy onto daughter cells. Single infected cell quickly gives rise to a large popu of baacteria carrying prophage virus. This mechanism enables the phage to propagate without killing the host cells.
Environmental signals like high-energy radiation and the presence of certain chemicals can induce the phage to transit from the lysogenic to LYTIC cycle. LYTIC CYCLE CONTINUES.
Why are bacteria not exterminated by phages?
- Natural selection favours bacterial mutants with receptor sites that are no longer recognised by a particular type of phage.
- Bacteria have restriction endonucleases that digest viral DNA that is recognised as foreign. The bacterial cell’s own DNA is chemically modified in a way that prevents attack by restriction enzymes. Just as natural selection favours bacteria with mutant receptor anr effective restrictiondenzymes, it also favours phage mutants that can bind the altered receptors or are resistant to particular restriction enzymes. The parasite-host relationship is in constant evolutionary flux.
- Many phages co-exist in their host cell via the lysogenic cycle.
What is haemagglutinin responsible for?
It is responsible for determining strain infection (which species it can infect and where)
Binds to specific receptor molecules. (sialic acid) on glycoproteins/glycolipids on CSM of epithelial cells of respiratory tract.
Facilitates the fusion of the viral envelope and the endosomal membrane.
What is the role of Neuraminidase?
It catalyses the hydrolysis of terminal sialic acid residues from the newly formed viral glycoproteins and from the host-cell membrane glycoproteins.
It facilitates the budding of the virus from the infected host cell and spread the infection to other cells.
What is the reproductive cycle of the influenza virus?
- Attachment. Haemagglutinin glycoproteins on the viral envelope recognise and bind to specific receptor molecules on CSM of epithelial cells of the respiratory tract, promoting viral entry into the cell.
- Entry. Enters host cell via endocytosis, forming an endosome. The viral envelope fuses with endosome membrane, exposing the capsid to digestion by cellular enzymes. This releases the viral RNA molecules, viral proteins and enzymes into the cytoplasm.
- Synthesis of viral components:
- The viral genome (-ve sense RNA) functions as a template for synthesis of complementary (+ve sense) RNA strands by viral RNA dependent RNA polymerase.
- The complementary RNA functions as mRNA which is translated into capsid proteins and viral glycoproteins. Vesicles embedded with viral glycoproteins migrate towards and fuse with the CSM. Viral glycoproteins become embedded on the CSM.
- Templates for replication of new copies of viral RNA genome (-ve sense) - Viral assembly. Capsid proteins enclose the viral genome and viral proteins. Capsid then assembles with viral glycoproteins during budding.
- Release. New virus buds from the cell, surrounded by the host cell surface membrane with viral glycoproteins.
What is a retrovirus?
These viruses are equipped with reverse transcriptase, which uses its viral RNA as template for synthesis of DNA. Viral reverse transcriptase usually synthesises a double stranded DNA from a single stranded RNA.
HIV causes Acquired Immune Deficiency Syndrome.
HIV is an enveloped virus that contains two identical molecules of single-stranded RNA and important enzymes like reverse transcriptase, integrase and protease.
What is the reproductive cycle of HIV?
Attachment: gp120 glycoproteins on viral envelope recognises and binds to specific receptor molecules on CSM of helper Tcell
Entry: Virus envelope fuses with the CSM. Capsid proteins are degraded by host cell enzymes, releasing viral RNA.
Integration: Reverse transcriptase catalyses the synthesis of a single DNA strand complementary to the viral RNA. The viral RNA is degraded and reverse transcriptase catalyses the synthesis of a second DNA strand complementary to the first. Newly synthesised double stranded viral DNA then enters the cell’s nucleus and integrates, as a provirus, into the host cell DNA via the action of integrase.
Synthesis: proviral genes are transcribed into RNA molecules by host’s RNA polymerase. They function as viral genome for next generation.
mRNAs, which are translated into both viral and capsid proteins and viral glycoproteins. Vesicles embedded with viral glycoproteins migrate towards and fuse with the CSM. Viral GProteins are embedded on CSM.
Maturation: Capsid proteins enclose the viral genome and proteins, assembling with viral glycoproteins during budding.
Release: New virus buds from the cell, surrounded by the host cell surface membrane studded with viral glycoproteins.
What is antigenic drift and shift?
Drift refers to the process by which varies genetically in minor ways from year to year. Spontaenous point mutations in viral genes cause small differences in the structure of the viral surface antigens.
Shift refers to a major change in the surface antigens of virus, caused by a reassortment of their segmented genome.
How does antigenic drift occur?
RNA viruses must replicate their genomes using VDRNApol, which lack proofreading ability unlike DNA pol. RNA viruses thus have a greater rate of mutation that DNA viruses.
For influenza, point mutations encoding H and N happen continually over time as the virus replicates.
This can cause epidemics.
For HIV, drift occurs dued to error-prone reverse transcriptase mutates the genes in gp120 and gp41.
