Evolution of Viruses Flashcards

Question

Most influenza viruses are non-virulent for poultry and cause locally restricted viral infection of the intestine -> Classical avian flu (Geflügelpest)

Answer 1

- Pathogen: highly virulent influenza A strains - In contrast to “normal“ influenza virus which replicates in the gut the virulent form displays a systemic infection Highly virulent avian flu virus: Cleavage site in HA mutated (now poly-basic); thus HA can be cleaved after synthesis by the cellular protease Furin in the Golgi - released viruses are infectious without further activation steps Systemic infection: spleen, liver, lung, kidney, CNS -> lethal

Answer 2

Myxomatosis virus isolated in Brasil from American tapeti (Sylvilagus brasiliensis) Australia 1950 ies: Release of Myxomatosis-virus to control population of European rabbit introduced by immigrants Spread by fleas and mosquitos (passive, no replication in Arthropodes), 90 - 99% lethal for european rabbits 1. year: Mortality rate 99,8% Efficient killing of rabbits 2. year: Mortality rate only 25% Rapid selection of adaptive mutations in the virus (and the host) Attenuated virus variants / host population in between only a few years Later years: Mortality lower than birth rate of rabbits Adaptation between host and virus!

Answer 3

Which was the predominant virus form? Viruses that were moderately virulent. Why? Viruses that were too much attenuated had a too low titer in the skin. Therefore, the passive transmission by the mosquito did not work efficiently. Highly virulent viruses kill the host too quick, so the time span arthropodes can get infected is too short for an efficient spread.

Answer 4

Infection of rabbits under laboratory conditions with a defined Myxoma virus which killed about 89% of the rabbits collected at Lake Urana prior to release of the virus Rabbits collected after the first two epidemics behaved the same However, rabbits colleced after the fourth epidemic showed only 50% mortality Lab experiments were sometimes missleading. Why? Higher survival rates when ambient temperature is higher (38°C)! Armsrace still ongoing between virus and host: viruses collected in 1990 were more virulent than the original 1950 viruses in non-resistant rabbits

Answer 5

... in 1950, after a smallpox-like virus found in South American rabbits turned out to kill the European relative, Australian authorities released the virus into the wild, cutting the rabbit population by 99%. A few years later, the virus, called myxoma, was released in France and eventually spread to the United Kingdom. The result was “an opportunity to trace host-pathogen arms races right in front of our eyes,” says Jia Liu... ...tracked down specimens of U.K., Australian, and French O. cuniculus collected by museums prior to the virus's introduction. They sequenced all the genes and other DNA that might influence the body's immune defenses and compared the results with sequences from modern rabbits living in the same places. The comparisons revealed changes in many genes, usually a shift in the frequency of particular versions, or alleles, of a gene. Strikingly, half of the changes were shared by the rabbits in all three countries—evidence of parallel evolution. One allele shift affected the rabbits' interferon, a protein released by immune cells that sounds the alarm about a viral attack and helps trigger an immune response. Compared with preinfection rabbits, modern rabbits make an interferon that is better at responding to the biocontrol virus, the researchers found when they added different versions of the protein to rabbit cell lines. Calicivirus Rabbit hemorrhagic disease RHD First description1984 in China; release in Australia by “lab accident“ in 1995 2008: rabbit numbers in Australia are increasing again

Answer 6

* Passaging of viruses on cultured cells (especially cells derived from non host species) may lead to attenuated virus variants with decreased virulence (e.g. by restricted tissue tropism). * Inefficient replication or receptor binding * Example: Poliovirus- live vaccine strains

Answer 7

Therefore only the killed Salk vaccine is used nowadays in Europe and the USA

Answer 8

- 1999 last case of poliovirus type 2 infection; since 2015 no vaccination with Sabin type 2 - in people vaccinated since, no immunity against Poliovirus type 2; - vaccine-derived poliovirus type 2 cases are problematic in Africa, Afghanistan, Pakistan, Malaysia Strategy - Cre element in 5 ́UTR (not present in any wt picorna virus, therefore no genetic exchange of 5 ́UTR possible) - Stable mutation in stem V (no reversion due to deleterious intermediate) - Mutations lowering the error rate of 3Dpol and lowering the propensity for template switching stabilze the virus

Answer 9

* two different forms of infection 1. Infection of non-pregnant animals („acute infections“) * (fever, diarrhea, respiratory symptoms, thrombocytopenia) * mostly clinically inapparent 2. Diaplacentar infection: * misscarriage, malformations * persistent infections (PI animals) Important: stage of gestation

Answer 10

1. Infection with noncp BVDV (day 30-100 of gestation) 2. persistent infection with noncp BVDV (immun-tolerance) -> Mutation (1-2 years) 3. Isolation of noncp and cp BVDV (virus pair) -> Mucosal Disease (100 % lethal) -> 1-2 % of cattle population around the world

Answer 11

A. Northern Blot analysis B. RT-PCR C. Nucleic Acid sequencing Identification of cellular mRNA sequences in viral RNA genomes!

Answer 12

Identification and characterisation of cellular insertions in the viral RNA genome - ubiquitin - NEDD8 - GATE-1 -> Common theme: Substrates of cellular proteases! Consequences of identified genome variations -> altered cleavage profile of polyprotein, upregulation of replication -> cytopathogenicity, lethal disease in PI animals RNA-Recombination – cytopathogenicity - Mucosal Disease

Answer 13

Ubiquitin-insertion serves as processing signal for cellular ubiquitin-specific proteases in viral poly protein Further cellular insertions with analogous function: - Ubiquititin-like proteins (e.g. SUMO) - Proteins with ubiquitin-like fold NS2-3: no replicase component NS3: essential replicase component Effect of ubi-insertion: - deregulated, complete NS2-3 cleavage - deregulated RNA replication - viral cytopathogenicity and disease

Answer 14

1. "Template switching" of RdRp during viral RNA-replication 2. "breakage and ligation" of viral RNA genome: independent of viral replication!

Answer 15

RNAs with deletions may arise by recombination Defekte interfering virus genomes accumulate during high titer replication of (-) and (+)strand RNA viruses Shorter RNA replicates faster -> competes /interferes with complete genomes for RNA-synthesis machinery -> May be packed into virus particles, if missing proteins are complemented by a complete helper virus Beneficial: High „multiplicity of infection“ (m.o.i.) Role in pathogenesis and chronicity (SSPE/chronic Measles virus infection)? Problem in vaccine production (Influenza virus) Potential antiviral strategy?

Answer 16

Discussion: Effectiveness of vaccines and laboratory diagnostics (RT-PCR, Ag-/Ab-detection)

Answer 17

- non homologous deletion Critical mutations: Deletions in accessory genes like ORF7a or 7b Upon mutation in infected cat-> FIP virus (mutant) kills cat

Answer 18

- lethal disease - peritonitis and/or pleuritis - or granulomatosis in multiple organs Cross section of a kidney from a cat with dry FIP. Numerous granulomatous lesions are seen on the capsule of the kidney and extending downward into the parenchyma

Answer 19

Definition Escape from the immune response of the host (to establish chronic infections) Examples: Lentiviruses (e.g. HIV), HCV

Answer 20

1. Change of host range: HIV, Parvoviruses, Influenza viruses, SARS-Virus 2. Change of virulence: Influenza viruses, BVDV, FeCV/FIPV 3. Persistent infections: HIV, HCV

Answer 21

1. Genetic variability: Change of virulence adaption 2. Correction of lethal mutations: genome conservation, repair of viral genomes, genetic stability 3. Generation of "novel" viruses

Answer 22

Recombination is one strategy to eliminate errors occuring during RNA-synthesis (negative or lethal point mutations or deletions) -> Repair of viral RNA genomes especially important for viruses with large RNA genomes (e.g. coronaviruses)

Answer 23

Example 1 (alphaviruses): Eastern equine encephalitis virus (EEV) + Sindbis virus  Western equine encephalitis virus (WEEV) Beispiel 2: FCoV-1 + CCV ---> FCoV-2 Further examples WEEV FCoV-2 Poliovirus (inter- and intratypic) MKS-Virus Enterovirus Dengue Virus ...

Answer 24

Example 1: Discontinuous transcription of subgenomic RNAs (Nidovirales) Intramolecular RNA recombination during minus- strand-synthesis of Nidovirus subgenomic RNAs Non contiguous genomic sequences are fused Example 2: Cap snatching of Orthomyxoviruses (e.g. Influenza virus) Viral polymerase elongates cell derived mRNA fragment thereby fusing cell-derived and viral sequences

Answer 25

Because bacteriophages generally parasitize only closely related bacteria, it is assumed that phage-mediated genetic exchange occurs primarily within species. Here we report that staphylococcal pathogenenicity islands, containing superantigen genes, and other mobile elements transferred to Listeria monocytogenes at the same high frequencies as they transfer within Staphylococcus aureus. Several staphylococcal phages transduced L. monocytogenes but could not form plaques. In an experiment modeling phage therapy for bovine mastitis, we observed pathogenicity island transfer between S. aureus and L. monocytogenes in raw milk. Thus, phages may participate in a far more expansive network of genetic information exchange among bacteria of different species than originally thought, with important implications for the evolution of human pathogens.

Answer 26

- 1 g of human feces contains more than 109 virions; many phages - viral populations differ greatly between humans - correlates in part to differences in microbiome - 2.5 years sampling from one person; sequencing of DNA - 478 DNA virus sequences; 87% of the DNAs showed no overlap with previously identified viruses - viral populations themselves undergo in those 2.5 years a rapid evolution, giving rise to new phage species The healthy human gut virome consists mainly of long-term resident phages that can rapidly evolve, contributing to variation between individuals.

Answer 27

Example for genomic exchange between virus and host Polydnaviridae (e.g. bracoviruses) (from polydisperse DNA virus) -> 10-30 circular dsDNAs up to 300 kbp - virus-like particles observed in the ovaries of numerous species of parasitic wasps (parasitoids); in tens of thousands of wasp species - present in all females of all affected species, suggesting vertical transmission - part of the viral proteins for packaging not encoded by the virus but by the host (Bézier et al., Science 2009; 323:926ff) - wasp host encodes for the genes missing for viral packaging: 22 putative nudivirus gene homologs in the wasp genome, including12 core genes that are also present in the related baculoviruses - those genes are expressed in the eggs of the wasp which are injected into caterpillars, which is paralyzed, and new wasps develop - considerable antigenic and genetic similarity between the venom genes of the wasp and polydnaviral genes -> virus genes support the parasitoid survival in the caterpillar So far viruses have been typically seen as either parasites or commensals; we must now recognize a potential for obligatory mutualism (kind of symbiosis).

Answer 28

- endogenic retroviruses (ERVs) in the genome of the eukaryotic host Endogenous retroviruses regulate periimplantation placental growth and differentiation - envelope proteins of endogenous Jaagsiekte sheep retroviruses (enJSRVs) regulates trophectoderm growth and differentiation in the periimplantation conceptus (embryo/fetus and associated extraembryonic membranes) Proof for functional role: - antisense oligos against ERV mRNA injected into onceptus trophectoderm retarded trophectoderm outgrowth, inhibits cell differentiation and leads to loss of pregnancy ERVs play fundamental roles in placental morphogenesis and mammalian reproduction