Lecture 2 Flashcards

1
Q

What are the 10 Virus replication phases?

A
Attachment
Penetration
Uncoating of viral material
Transcription of mRNA
Translation of early proteins
Replication
Transcription of mRNA
Translation- late proteins
Assembly of virions
Release of virus from cell
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2
Q

How does the herpes virus acquire its envelope?

A

Different viruses acquire their envelope from different membranes in the host cell: cytoplasmic membrane, nuclear membrane, ER membrane. As the virions are being assembled, they move toward the membrane that is required (determined by the virus). The virus envelope is essentially a modified cell membrane, meaning that the host cell’s membrane becomes modified by the insertion of virus-encoded proteins during the replication process.
Ex. herpesvirus acquires an envelope during the budding process (release from the cell), therefore the envelope is a modified cytoplasmic membrane.

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3
Q

What is the envelope?

A

modified host cell membrane that contains the anti-receptors to recognize host cell receptors,

mediates the attachment phase of viral replication

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4
Q

What is the difference between anti receptor and receptor?

A

The anti-receptor is a 3D structure on the virus (the anti-receptor is a region on the HA peplomer), whereas the receptor is a 3D structure on the host cell.

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5
Q

4) Describe the significance of sialic acid-galactose linkages of cell receptors with respect to species specificity of influenza viruses.

A

The influenzavirus HA anti-receptor recognizes/binds to sialic acid residues on the host cell receptor.

Cell receptors of various species contain sialic acid and galactose that are linked to one another by different conformations. Species specificity is due in part to the distribution of cells with these different linkages throughout the host.
For example, α-2,3 linkages are found in avian receptors. α-2,6 linkages are found in mammalian receptors. The variation in linkages causes slightly different conformations of the host cell receptor- these changes are recognized by the viral anti-receptor and contributes to species specificity of influenzaviruses (there are other factors that also help determine host range).

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6
Q

What is the viral capsid?

A

protein structure that protects the viral genome

may be enveloped, non-enveloped, depending on the virus family

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7
Q

What is viral symmetry?

A

refers to the geometrical relationship between the capsid and genome

two types icosohedral or helical

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8
Q

What is icosohedral symmetry?

A

NA loosly contained within a polyhedron that has either 5,3, or 2 fold axis of rotation

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9
Q

What is helical symmetry?

A

capsid is closely associated, sometimes directly attached to the NA,

looks like a herringbone on EM

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10
Q

What is the difference between a capsomere and a protomere?

A

protomer is the basic structural component of the viral capsid, whereas a capsomere is simply a morphological unit that can be clearly discerned by EM

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11
Q

What is a protomere?

A

described as being the basic building block of the capsid, formed by distinct polypeptides

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12
Q

What is a capsomere?

A

The term capsomere is sometimes referred to as the basic structural unit of the capsid, but this is incorrect (the protomer is the basic structural unit). For some viruses, the protomers are arranged in a manner that form clearly distinct morphological units, therefore the protomer also constitutes the capsomere. The capsomere may be made up of a single protomer, or of several protomers coming together

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13
Q

T/F

The protomer is always the basic structural unit, and may or may not also be the basic morphological unit (capsomere)

A

TRUE

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14
Q

What are structural proteins function, give an exapmple?

A

Structural proteins are matrix proteins that provide support for virus envelopes.

Ex. rhabdoviridae (rabies, vesicular stomatitis virus) – matrix protein contributes to the rigid structure of the virion

-influenzavirus – the matrix protein provides a basis for glycoproteins that are associated with the envelope to bind and stabilize – this may contribute slightly to the shape of the virion.

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15
Q

What are structural proteins function, give an exapmple?

A

Non-structural proteins do not contribute to virion structure and instead function as enzymes or regulatory proteins.

Ex. influenzavirus: three nonstructural proteins comprise the polymerase complex: PB1, PB2, PA.

-poxviruses: have several proteins that are virokines/viroreceptors that function to suppress the host immune response.
Virokines: the counterpart of cytokines that belong to the virus. These can mimic host cell cytokines and may play a role in suppressing the host immune response.
Viroreceptors: bind to interferons sent out by dying host cells and interfere before they can reach their intended target (their target is usually other host cells – they want to bind and stimulate and antiviral state as a defense mechanism).

-rotavirus: Non-structural protein 4 (NSP4) acts as an enterotoxin and contributes to the diarrhea caused by rotaviruses

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16
Q

Draw & accurately label a diagram of influenza virus, and describe the function of the proteins and what proteins are used for classification at the “type” and “sub-type” levels.

A

DO IT but i doubt this is on the test bc its on the computer

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17
Q

Define Nucleocapsid protein (NP)

A

internal protein that forms the nucleocapsid.

*used for type classification (ex. type A, B, C)

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18
Q

Define Matrix protein 1 (M1

A

internal protein that stabilizes the virus envelope (may contribute to virion structure).

*used for type classification (ex. type A, B, C)

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19
Q

Define Hemagglutinin (HA)

A

envelope glycoprotein that contains the antireceptor region.

There are 16-17 antigenically distinct HA proteins.

*used for subtype classification (ex. H1N1).

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20
Q

Define Neuraminidase (NA)

A

envelope glycoprotein.

There are 9 antigenically distinct NA proteins.

*used for subtype classification (ex. H1N1).

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21
Q

Define PB1, PB2, PA

A

nonstructural proteins that form the polymerase complex

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22
Q

10) Describe how nomograms are used to name specific influenza virus isolates.

A

Nomograms describe individual influenza virus isolates based on their type, host species, location, date, and subtype.
Ex. If a type A, subtype H1N1 influenza virus was isolated from a pig in Iowa in the year 2015:
A /swine /Iowa /2015 /H1N1

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23
Q

What does strandedness mean?

A

Strandedness – single vs. double vs. 2 strands covalently linked. This characteristic of viruses is important in understanding how they replicate and which cells they might infect, etc.

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24
Q

Give an example of how stranded effects virus? Parvo Virus

A

Parvoviruses are very small single-stranded viruses. Because they are single-stranded, they cannot be transcribed directly by cellular transcriptase. They are very small viruses and therefore do not carry their own polymerase – they rely on the host cell machinery for this. They tend to infect host cells that have a high mitotic index (rapidly dividing cells) because if the virus happens to be in a cell that is starting to undergo division, there is going to be a lot of DNA-dependent DNA polymerase (the host cell uses it to replicate its own genome). This cellular DNA-dependent DNA polymerase can use the single strand of viral DNA to generate a template to make a double strand, which can then be expressed and used to replicate the virus.

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25
Q

What is configuration?

A

c. Configuration – the genome can take on different configurations (e.g. linear, circular, segmented) that can play a role in determining viral features.

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26
Q

How does configuration effect replication?

A

i. Ex. influenzaviruses have a segmented genome, which is a huge factor in antigenic shift and the emergence of new subtypes. Genetic reassortment is possible with the segmented genome, resulting in progeny viruses having different combinations of genetic segments donated by the two parent genomes. Each new subtype has potential to cause an outbreak of pandemic proportions and requires a new vaccine

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27
Q

What are the three sense (s) ?

A

– this property refers ONLY to ssRNA viruses.

positive

negative

ambisense

28
Q

What is positive sense?

A

the genome can serve as “messenger” (i.e. mRNA) and be translated.

(you can open the virus, extract the ssRNA, put it in a test tube with the enzymes and components necessary for translation, and it will be translated)

29
Q

What is negative sense?

A

Negative sense genome: the genome cannot serve as messenger, therefore will not be translated on its own when exposed to the necessary translation enzymes.

30
Q

What is ambisense?

A

Ambisense genome: one part of the genome can serve as messenger right away but the other part has to be converted from negative to positive sense and then translated.

31
Q

What does size have to do with the virus?

A

viruses vary greatly in size and therefore have to utilize different expression strategies to produce sufficient proteins. Small viruses use many special expression strategies and rely on the host cell for certain enzymes or replication hardware. Large viruses such as the poxviruses do not require anything from the host cell other than an E source because it codes for everything itself on its large genome.

32
Q

Define Open reading frame (ORF)

A

the segment of the genome that contains the genetic message for the protein to be expressed

33
Q

Define TATA box

A

a series of T / A nucleotides in a DNA genome that indicates an ORF – serves as a type of promoter

34
Q

Define Enhancer

A

a sequence of the genome that binds regulatory proteins and allows them to interact with transcription factors at the promoter sequence, activating transcription

35
Q

Define promoter

A

a sequence of the genome that is located near the transcription initiation site of an OR

36
Q

Define transcription initiation site

A

site where transcription starts on an ORF

37
Q

Define termination signal

A

the site where transcriptase drops off of the segment (stops transcribing) and the completed mRNA is generated

38
Q

What is constitutive splicing?

A

introns removed, exons joined in same order they occurred in the pre-mRNA trnascript

39
Q

What is alternative spicing?

A

introns removed in the same way, but exons are joined together in different order/combination

40
Q

How does shifting reading frames effect expression?

A

ribosome jumps either forward/backward a space in sequence and then moves on, resulting in a different reading frame

41
Q

What is leaky scanning?

A

the ribosomes selects an alternate start codon by passing over the first codon available resulting in a different sequence

42
Q

What is post-translational modification?

A

once mRNA is created, it is translated to produce one big polyprotein. This polyprotein contains regions that have protease activity – this allows for self-cleavage, and the result is multiple smaller polypeptides (each with a different function).

43
Q

Describe genomic maps and their usefulness (with examples).

A

Genomic maps indicate what regions of the viral genome encode specific proteins. You can use a genomic map to identify a specific protein and trace them back to the genome to figure out where the genetic information is contained. It is also helpful for comparing genomes of viruses within a family and seeing similarities/differences in specific genes

44
Q

What is a virus lineage?

A

represents all of the virus strains that have descended from a common ancestor

45
Q

What is a clade?

A

refers to a group of viruses that have all emerged from the same recent common ancestor

46
Q

Why is a phylogenetic tree

A

Phylogenetic trees reveal degrees of similarity among viruses within families and also between virus families. They are typically generated based on a specific gene (usually the gene in which there is the least amount of variation within the family). These trees show the relative degree of relationship between the viruses being compared. Phylogenetic relationships can be useful in determining epidemiology and source location of a particular virus strain

47
Q

Use west nile virus to explain phylogenetic trees

A

Ex. WNV: WNV emerged in the US on the east coast in the NY metro area around 1999. Different isolates were discovered, and when compared on the phylogenetic tree they are very similar: all of these viruses have originated from a common ancestor (i.e. are within the same clade). When compared to the isolates from Israel, you could conclude that it is very likely the NY virus strains originated from somewhere in the Middle East.

48
Q

Describe determinants of host range using the mouse reovirus as an example.

A

The mouse reovirus is a model used to demonstrate the role of the cell receptor in disease manifestation. It has three major antigenically distinct serotypes that are determined by a surface protein that also acts as the antireceptor. Comparing serotype 1 to serotype 3, subtype 1 can produce encephalitis because it attaches to neurons. Subtype 3 does not cause encephalitis, but instead infects the cells of the ependymal that line the ventricles/canals, causing a local inflammation that blocks the pathway of flow of CSF in the brain, leading to hydrocephalus. This inflammation also affects the pituitary gland and causes retarded growth of the host. This example demonstrates that an identical virus with different serotypes can cause different clinical manifestations. This can be considered a determinant of host range because different host species will have different receptor populations and a similar effect will be observed (one subtype can infect a particular species while a different subtype cannot).

49
Q

18) Describe determinants of host range using HIV as an example.

A

The HIV virus (Retroviridae) demonstrates a similar concept of cell tropism determined by cell receptors. HIV virus has one antireceptor specific for the CD4 receptor on the host cell. It also has a second antireceptor that is specific for either the CXCr-4 receptor present on host T helper cells, OR the CCr5 receptor found on host M0 – presence of one of these receptors or the other determines virus strain. HIV strains with the antireceptor specific for CD4 and CCr5 are more likely to affect the brain than viruses with antireceptors specific for CD4 and CXCr4 because the CCr5+ strains infect M0 that can carry the virus into the CNS. CC4+ strains can also infect the microglia (resident M0) within the brain.

50
Q

What is antigenic shift?

A

occurs via genetic reassortment of an HA and/or NA gene and results in a change in the subtype of the virus such that the new subtype is different than the circulating virus (ex. H1N1  H3N1).

51
Q

What is antigenic drift?

A

is caused by a change in the antigenicity associated with the receptor – there is a change that affects the 3D structure of the antireceptor region of the HA without changing subtype. This can occur via mutation of a gene that leads to AA substitutions that lead to a change in the conformation of the antireceptor (receptor binding pocket) – most commonly, multiple mutations occur that cumulatively lead to a change in antireceptor conformation. The subtype of the virus remains the same, but the antireceptor has changed.

52
Q

T/F

In both antigenic shift & drift, the original vaccine may not be effective in inducing protective immunity against the new circulating virus. A new vaccine will have to be developed in order to be effective in both cases

A

True

53
Q

Describe why a specific virus can cause different clinical manifestations in the same host

A

One virus can cause different clinical manifestations in the same host because they might have different strains that have tropisms for different cells, based on the population of antireceptors present on the virus surface. If the antireceptors are different between strains, then the virion will likely recognize and infect distinct cell types. (refer to #18).

54
Q

What is positive staining?

A

take infected tissue and create thin sections, then stain with an electron dense salt (ex. osmium tetroxide) that binds directly to protein. When examined with EM, the electrons will not be able to pass through the proteins bound to osmium tetroxide because they are electron dense, and therefore these areas will appear dark. In contrast, the electrons will pass freely through areas without protein and these areas will appear white

55
Q

What is negative staining?

A

viruses are negatively stained, meaning that the electrons from EM can pass through the virion and strike a screen that fluoresces. The virus-infected material under study is mixed with phosphotungstic acid (PTA), which fills in the areas on the surface of the virus that are not occupied by virus proteins. The suspension containing prepared virus and PTA is sprayed onto a small copper grid, then inserted into the EM and examined. The PTA-containing areas appear dark, and the rest of the virus (that is covered by protein) appears white.
Negative staining can be used for examining diarrhetic feces, fluid from vesicular lesions, and virus grown in cell culture.

56
Q

Avian Influenza

A

Family: Orthomyxoviridae

Genus:

Clinical signs: high/low path; can cause sudden death, prodromal syndromes, like do not survive >48hours (high path)

Species: chickens/turkeys

Structure: enveloped nucleocapsid, helical, segmented ss-RNA

Transmission: respiratory/fomites

Unique info: “Foul plague.” HA is the main determinant of virulence for this.

57
Q

Pacheco’s Disease Virus

A

Family: Herpersviridae

Genus: Herpesvirus

Clinical signs: acute death, bright yellow urate with scant feces, lethargy, diarrhea, ruffled feathers and tremors in the neck, wing, and legs

Species: psittacines

Structure: enveloped, icosohedral, linear DNA

Transmission: direct contact

Unique info: Replication occurs in the nucleus of a cell

58
Q

Contagious ecthyma virus

A

Family: Poxviridae

Genus: parapoxvirus

Clinical signs: orf virus, pustules on lips/muzzle

Species: sheep/goats

Structure: large oval/brick shaped, no symm, dsDNA

Transmission: contact

Unique info: Seriological cross reactivity occurs within genera, but not cross genera. Resistance outside of host is great

59
Q

Vesicular stomatitis virus VSV

A

Family: Rhabdoviridae

Genus: vesiculovirus

Clinical signs: Salivating and fever =1st sign in horses and cows, Lameness = 1st sign in pigs. Lead to vesicular lesions on the tongue, teats, oral mucosa, and coronary bands

Species: cattle, horses, pigs

Structure: bullet shaped, enveloped, ssRNA

Transmission: arthropod/contact

Unique info: diff for FMD virus, stable in environment

60
Q

Rabies virus

A

Family: Rhabdoviridae

Genus: Lyssavirus

Clinical signs: Infection virtually always results in death. Generally have to be bitten by a rabid animal. Either have furious rabies or dumb rabies

Species: all mammals

Structure: bullet shaped, enveloped, ssRNA

Transmission: animal bite

Unique info: Virtually all infected animals eventually die; must be transmitted via bite; Cause negri bodies

61
Q

CAV 1 and 2

A

Family: Adenovirus

Genus: mastadenovirus

Clinical signs: asymptomatic or respiratory disease; can be systematic, peracure, acute and mild phases

Species: canines

Structure: large to medium nucleocapsids, dsDNA, nuclear inclusions

Transmission: respiratory, fecal/oral

Unique info: retains infectivity outside host for several months, depending on conditions

62
Q

Canine Distemper Virus

A

Family: paramxyoviridae

Genus: morbillivirus

Clinical signs: highly contagious, acute febrile dz, signs depend on strain, host age/immunity, environmental stresses; 50% cases subclinical, mild is often confused w/ kennel cough; severe is febrile w/ systemic spread and profound leukopenia

Species: canines

Structure: pleiomorphic, enveloped, helical, ss-RNA

Transmission: respiratory, contact, fomites

Unique info: most are sub acute infections, also seen in lions, cheetahs, etc, mild disease can be confused w/ kennel cough

63
Q

Rotavirus

A

Family: Reovirus

Genus: rotavirus

Clinical signs: White scours or milk scours. Feces is voluminous, soft to liquid, and contains a large amount of mucous. Usually only seen in animals 2-8 weeks of age

Species: Cattle, sheep, goats, horses, dogs, cats, rabbitts, mice, birds

Structure: Medium sized, naked, multi-layered capsid, DS segmented RNA genome

Transmission: fecal oral

Unique info: Known for retaining infectivity for several months outside of the host. Major cause of diarrhea in intensively reared farm animals.

64
Q

TGE- transmissable gastroenteritis virus

A

Family: Coronaviridae

Genus: Coronavirus

Clinical signs: Vomiting, dehydration, profuse watery yellow diarrhea, esp in young piglets.

Species: swine

Structure: enveloepd, helical symm, ssRNA, club shaped

Transmission: Fecal/oral, respiratory, contact

Unique info: Death is uncommon in pigs 2-3 weeks old, asymptomatic in adults. Highly contagious

65
Q

Porcine epidemic diarrhea virus PEDV

A

Family: Coronaviridae

Genus: Coronavirus

Clinical signs: Diarrheal disease in piglets; Originally in Europe, Asia, and now NA.

Species: swine

Structure: enveloped, helical symm, ssRNA, club shaped

Transmission: Fecal/oral, respiratory, contact

Unique info: Similar to TGE; doesn’t infect suckling piglets

66
Q

Ebola Virus

A

Family: Flioviridae

Genus:

Clinical signs: Abrut onset of illness with non-specific signs. Fever, frontal headache, malaise and myalgia.

Species: Non-human primates are highly susceptible.

Structure: enveloped, ss - RNA, filamentous in nature

Transmission: unknown in nature, human is direct contact

Unique info: Highly feared zoonotic diseases. Highly lethal strains are associated with failures in both innate and adaptive immune responses