Viral Pathogens

Question 1

what is phage lambda

Answer 1

• enteric bacteriophage
• infects only E.coli
• study of phage yeilded fundamental discoveries in gene regulation - most notably the control of lysogeny

*injects DAN that is replicated in the bacteria

Question 2

how does phage lambda inject

Answer 2

• phage tail fibers bind to a specific outer membrane protein involved in uptake of maltose 9maltose proin) and injects its DNA into the cytoplasm

Question 3

structural characteristics of phage lambda

Answer 3

• lambda particle (wiron) is typical of tailed phages
• has capsid head with icosahedral preotin complex
• contrains linear dsDNA genome
• tail consists of sheath plus internal tube and tail fibers (helps in attachment to host cells)

*exact length of tail depends on “tape measure protein” (protein H)

*how it works is still unclear

Question 4

describe the lytic cycle of bacteriophage lambda

Answer 4

• phage hijacks host resources and proein synthesis machinery
• phage DNA replicated in the host cytoplasm to generate many progeny genomes
• structural proteins are assembled to form empty caspids, tails and tail fibres
• Porgeny genomes are packaged into capsid heads until the heads are ‘full’
• filled capsid heads are attached to tails
• late phage proteins: holins and edolysins are synthesized - lyse host cell to release the progeny

Question 5

what is the prophage state

Answer 5

-phage genome integrates in and replicates within bacterial host genome

Question 6

what are lysogens

Answer 6

• bacteria carrying the phage genomes and producing phage encoded proteins

Question 7

describe lysogeny and temperate phages

Answer 7

1. phage infects a cell
2. phage DNA becomes incorperated into the host genome
3. cell divides and prophage DNA is passed on to daughter cells
4. Under stressful conditions the prophage DNA is excised from the bacterial chromosome and enters the lytic cycle
5. Phage DNA replicates and phage proteins are made
6. New phage particles are assembled
7. the cell lyses, releasing the newly made phages

Question 8

how can engineered viruses be used to fight bacteria

Answer 8

• virus targets bacteria making it more susceptible to antibiotics

Question 9

what type of virus is influenza

Answer 9

negative (-) strand RNA virus

*bacteriophage was a ds DNA virus

Question 10

3 types of influenza

Answer 10

Influenza A: one of the msot common life threatening viruses

• approx 10% of pop are infected every year

Influenza B: narrower host range than influenza A - can cause serious disease but mutates much more slowly

INfluenza C: narrower host range than influenza A, cau cause serious disease but nto spread as easily

Question 11

WHat is H7N9

Answer 11

• influenza virus
• proposes a very serious desiease in high proportion of infected poeple
• not transmisible from person to perfom only bird to person
• big fear si the virus will mutate and be able to be transmitted from person to person
• future strain with seriousness of H7N9 and transmissibilty of H1N1 would be really bad

Question 12

diff between flu and a cold

Answer 12

• cold noramly caused by rona virus and flu by influenza

*diff viruses cause diff symptoms

Question 13

describe the structure of the influenza Viron

Answer 13

• flu virus has no geometic caspid
• shell of matrix proteins (M1) that surround the 8 linear (-) RNA chromosome segments each coated with nucleocaspid
• matrix shell is surrounded by a membrane envelope - derived from the host cells durign budding
• two major viral envelope proteins Hemagglutinin (HA) and neuraminidase (NA) stud the surface of the vrius

Question 14

describe the influenza virion genome

Answer 14

• 8 negative sense RNA segments (wavy purple thigns in picture)
• each coated with nucleocaspid proteins (NPs) *coating is the pink
• each encodes 1 protein
• 2 segments undergo splicing to encode 2 further proteins
• Each segment is packaged with an RNA dependent RNA polymerase (yellow dot on picture)
• During viral assembly of an infected hsot cell the segmetns are packaged randomly
• only 1 in 400 packaged virruses will be capable of subsequent infection (dont want to kill host too quick and illicit toos trong of an immune response right off the bat)

Question 15

what are the advantages of a segmented genome

Answer 15

• continuously changes antigenic determinants (why need diff flu shots each year) - by doing so it evades host adaptive immunity
• two or more strains can infect the same host cells

*if had two strains infeting at same time would have 16 individual segments that could package together so would need lots of antigens to fight against

• reassortment is why we cant regognize it from year to year
• segmented genomes allow for reassortment (between the different virus strains) of genetic info generating drastically new strains more quickly then viruses with non egmented genomes
• influenza also continuously acquires small mutation that can lead to new phenotypes with respect to drug resistance & host range

Question 16

why dont we need a new polio vaccine every year?

Answer 16

• poliovirus si not segmented

Question 17

what si the H protein

Answer 17

H also stands for Hemagglutinin - 18 HA subtypes

• forms a trimer complex (knobs) with each an N terminal fusion peptide
• allows for fusion of viral membrane with host cell membrane

Question 18

does deos HA allow for fusion of the viral membrane with host cell membrane

Answer 18

1. HA recognizes and bidns to host cell sialic acid- containing receptor (glycoprotein receptor)
2. Binding triggers uptake of virion by endocytosis
3. Endocytic vesicle acidifies and produces a conformational change in HA fusion peptide
4. Fusion of host and viral membranes can now take palce
5. Triggers release of the RNA genome cargo into host cytosol

Question 19

describe the steps of replication of the influena virus

Answer 19

*viral components must travel in and out of nucleus

*envolope proteins must be made and trafficked through the ER golgi

1. Viral (-) RNA segments (NP coated) are uncoated and enter the nucleus
2. attacked viral RNA polymerase synthesizes (+) strang RNA. the + RNA strand is used as mRNA or as templates for generating progeny -RNA
3. mRNA travels to cytoplasm for translation to viral proteins; viral coat proteins are embedded in host cell membrane
4. Genome packaging proteins, viral RNA polymerase, RNA segments coated with newly made nucelocaspids- exported to cytoplasm and translocate to host cell membrane
5. enveloped virus is released by buding and cleavage

Question 20

what enzymes are required for the relase of the virus

Answer 20

Viral encoded neuraminidase and host protease enzyme

Question 21

what are N proteins

Answer 21

• N (or NA) stands for neuraminidase

*there are 11 neuraminidase N variants

• envelope proteins and viral genome packages travel to cell membrane for packaging into new virions
• within the cell membrane envelope proteins assemble around the genome and matrix proteins
• virion then buds out of the host cell
• viral neuraminidase cuts the virion loose from the host cell to release it to extracellular space

Question 22

what determines if an animal will be susceptible to virus

Answer 22

• the ature of cell surface glycoproteins on host cells that bind HA (allowing endocytosis)
• presence of Host cellular protease to cleave the haemagglutinin

*note birds are the natural reservoir for influenza

• avian and human virus receptors are different - swine have both human and avian type receptors

Question 23

what is a major contributor to emergence of influenza

Answer 23

• wild and domestic birds in markets in china
• H7N9 does not easily spread from person to person but causes very high mortality in huamns - 1 in 3 die

Question 24

how do antibodies neutralize

Answer 24

• block viral infection of host cells - block entry and/or uncoating of cirus to release contents into host cytoplasm

*developing neutralizing monoclonal antibodies targeting a broad range of virus strains is a focus of many research labs

*vaccine strategy not yet been realized is how to target the immmune system to raise boradly neutralizing antibodies

Question 25

why do we need flu shots every year?

Answer 25

- drifting: ability of influenza virus (A and B) to mutate and change slightly \*usually becuase of RNA replication errors in HA and NA genes - Shifting: a big change in the structure of the flu virus, can be caused by creation of new virus species \*reassortment of genes from 2 diff viruses mixing in single host (usually pig(

Question 26

what can block neuraminidase

Answer 26

tamiflu