Virology Flashcards

1
Q

What is the most abundant life form in the human body?

A

Bacteriophages

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2
Q

What percent of our DNA is retrovirally infected?

A

8% and it accumulated through evolutionary time

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3
Q

What kind of diseases do viruses cause?

A
  • Acute (ex. cold)
  • Persistent (hepatic and herpes)
  • Recurrent (herpes)
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4
Q

Largest virus

A

Pox Virus (and more recently minivirus)

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5
Q

DNA virus v. RNA virus

A

We call it a “DNA virus” if there is DNA in the virion

We call it an “RNA virus” if there is RNA in the virion

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6
Q

How do viruses replicate?

A

Viruses replicate by de novo assembly of preformed components. virus cannot do anything on itself. They go into the cell, and tell the cell make more viruses.
So every one cell can make hundreds or thousands new viruses, there is no doubling, no mitotic events, simply a factory.

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7
Q

Attributes of Viruses

A

1) they are obligate intracellular parasites
2) They can influence behavior (sneezing or coughing) in order to spread but they have no means of locomotion, metabolism, or energy alone

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8
Q

Discovering viruses of Ancient Times

A

With the help of DNA sequencing, we can go back and look at mummies and determine what viruses they may have had (i.e. Hep B in mummies thought to have smallpox)

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9
Q

Viral diseases described in ancient sources

A
Rabies  
Measles
Smallpox
Polio
Yellow fever

Not until the description of DNA and RNA as the genetic material of life has the true nature of viruses become understood.

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10
Q

New Polio-like virus killing and paralyzing children

A

Acute Flaccid Myelitis, AFM

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11
Q

Biggest Concern for destroying us all

A

Flu or flu like virus because respiratory infections are the best way to rapidly spread something
(ex. measles)

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12
Q

Ways of Classifying Viruses

A
  • Phylogeny
  • Host Range
  • Disease caused
  • Tissues infected
  • Capsid structure
  • Presence or Absence of lipid envelope
  • Viral genome (RNA or DNA)
  • Segmented or non-segmented
  • single or double stranded
  • (+) sense or (-) sense
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13
Q

Where does a virus replicate its genome?

A

Either in the nucleus or the cytoplasm

RNA VIRUSES MAINLY REPLICATE IN THE CYTOPLASM

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14
Q

What protects the genome of a virus?

A

a protein coat called a CAPSID

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15
Q

Define Envelope

A

A lipid bilayer surrounding the capsid

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16
Q

Naked Virus

A

A virus with no envelope but do have a capsid.

Most naked viruses emerge from cells by cell lysis (bursting of the cell and kill the cell on its way out)

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17
Q

Where does the envelope in viruses come from?

A

They acquire a cell derived lipid bilayer by emerging from the cell via budding or from intracellular membranes.

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18
Q

Envelope Glycoproteins

A

transmembrane glycosylated proteins extending from the envelope which mediate attachment and entry of enveloped viruses into cells.

They are major determinants of cell tropism.

Envelope protein are major viral antigens.

They are usually trimers

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19
Q

Nucleocapsid

A

The capsid + the viral genome. Both naked and enveloped viruses have this

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20
Q

Enveloped viruses are sensitive to what?

A
  • Detergents
  • Heat
  • Drying
  • Bleach
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21
Q

Naked viruses are resistant to what?

A
  • Detergents
  • Heat
  • Drying
  • pH
  • Proteases
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22
Q

Icosahedral

A

most animal viruses have an icosahedral capsid

best way to maximize internal volume with minimal number of similar subunits

20 faces - equilateral triangles

12 vertices - with 5 fold symmetry

Pentons make up the vertices

Hexons make up the sides

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23
Q

Helical

A

Human helical viruses all have RNA genomes

e.g. influenza virus

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24
Q

Complex

A

Pox viruses - helical structure plus some other structures that are not understood.

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25
Q

Self-Assembly

A

When a critical concentration of viral components is reached at the proper location in the cell, these parts self assemble into viral subunits and then into whole viruses as it is a naturally energy efficient shape

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26
Q

Five Basic Structural Forms of Animal Viruses

A

1) Naked Icosahedral
2) Enveloped Icosahedral
3) Naked Helical
4) Enveloped Helical
5) Complex Viruses

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27
Q

Bacteriophage Structure

A

Icosahedral head, helical body which act like a syringe, they inject their nucleic acid into the cell, and they get this feet that look like space ship.

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28
Q

Viral Replication, or the infectious cycle

A

From one virus binding to a cell to the production of new infectious viruses

Early:
Adsorption - binding to cell - the host range of the virus is often controlled here
Penetration - enters cell
Uncoating - releases viral genome within cell
Migration of genome to nucleus (many viruses, not all)

Late:
Replication of viral nucleic acid - replication of genome (DNA or RNA) Can happen in the cytoplasm or the nucleus, depending on the virus.
Transcription from genome yielding mRNA
Translation of mRNA to produce viral proteins
Assembly - virions constructed from viral proteins and nucleic acids
can happen in the nucleus or the cytoplasm, or a combination of the two
Release of virions - via budding or cell lysis
Spread to new host - transmission of virus to new cell or to new individual

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29
Q

Antigenic Sites

A

determine serology; antibodies NEUTRALIZE virus

30
Q

Structure of Env Gylcoprotein

A

Typically made up of a transmembrane domain & an ectodomain (an outer/ outside the virus domain). It is the ectodomain that does the binding to the cell. And, it is the transmembrane that often mediates the fusion with the target cell.

31
Q

Enveloped Virus Entry/Fusion

A

Fusion can happen at the cell surface (e.g. HIV) or the virus can first enter the cell in an endosome, then fuse with the membrane of the endosome to release the genome into the cell (e.g. influenza virus)

32
Q

Naked Virus Entry

A

1) They use spikes and bind similar to envelopes and form endosomes (like adenoviuses)
2) they form endosomes on the outside of the cell. they won’t split open the endosome and deliver everything into the cytosol. In the case of poliovirus: they squirt their genome through the endosome into the cytoplasm. This is a way of helping to keep the cell from forming an intracellular immune response.
3) instead of delivering the genome into the cytosol, in this example it is delivering the genome right through the nuclear envelope; where it actually cracks open the endosome & in this case it also entering the nucleus.

33
Q

Viral Replication

A

First of the “late stage” events

Viruses must replicate their genomes using either a
cellular polymerase or a viral polymerase, or both. It must also make mRNA to generate proteins and new virions.

34
Q

Replicase

A

A viral nucleic acid polymerase

35
Q

What makes a good drug target for viruses?

A

When a virus uses its own enzyme to do something

36
Q

What makes a bad drug target for viruses?

A

When a virus uses a cellular enzyme since it is needed by the cell to do its normal functions and inhibiting a cellular enzyme can be toxic

37
Q

the flow of genetic information is in one direction

A

dsDNA → mRNA (single (+) strand) → Protein

transcription in nucleus and translation in cytoplasm

38
Q

DNA-dependent DNA/RNA polymermase

A

uses DNA as a template to create either more DNA (replicate dsDNA) or to generate mRNA which is found in all cells

ex. RNA polymerase II

39
Q

RNA-dependent RNA polymerase

A

use RNA as a template to generate RNA, or to generate DNA*

If a virus wants to use RNA as a template it must make its own enzyme.

40
Q

Which viruses need their own replicases? (generally)

A

ALL RNA viruses are going to have to have their own replicase. ALL of them

41
Q

(+) ssRNA virus

A

This might function as mRNA.
The cell can use this to make viral proteins.
The cell cannot make new genomes from it, so one of those viral proteins must be a replicase. So the replicase might not HAVE TO be packaged into the virions.

42
Q

(-) ssRNA virus

A

The cell cannot use this.

The virion must deliver a replicase enzyme into the cell to generate (+)RNA (mRNA)

43
Q

dsRNA virus

A

The cell cannot use this.
The virion must deliver a replicase enzyme into the cell to generate (+)RNA (mRNA)
Cell pattern recognition receptors in your cells that are there to say ”is there double-stranded RNA in the cell and if there is let me die because there is a virus among us.” So, this will often trigger cell death so the virus often has to protect itself very well from triggering those responses

44
Q

Where do DNA viruses replicate?

A

Most DNA viruses replicate in the nucleus where they can use the cell’s machinery for:

DNA replication (though most DNA viruses encode their own DNA polymerase)

DNA ➔ RNA transcription - regulated by transcription factors

RNA processing - a complex process only the cell can perform

Some DNA viruses induce cell proliferation and can cause cancer.

Herpes viruses encode some enzymes to allow them to replicate in neurons that are not proliferating - a drug target.

45
Q

What DNA virus does NOT have to replicate in the nucleus?**

A

Pox Virus

46
Q

Retrovirus Replication

A

Using reverse transcriptase, it converts (+) ssRNA into dsDNA, it integrates into the chromosomes, makes messenger RNA as if it were a cellular gene, and then you make new viruses.

47
Q

Assembly, maturation and release

A

When a critical concentration of proteins accumulate, they self assemble into viral subunits or higher order structures.

Assembly of subunits or virions occurs in specific sites within the cell, the nucleus, the ER/Golgi, the cytoplasm, the plasma membrane.

Many viral proteins are generated first as a polyprotein which is then cleaved into mature proteins by either a viral or a cellular protease.

Assembly and maturation are attractive targets for antiviral drug development.

48
Q

What do protease inhibitors do?

A

they prevent a cell that is infected from making new viruses that are infectious.

49
Q

Naked Virus Release

A

all of the little viral particles continued to accumulate within the cell. So, most naked viruses crack open the cell. Some leave without killing the cell, but most of them kill the cell.

50
Q

Patterns of viral infection and disease

A

Acute Infection

Latent Infection

Chronic Infection

51
Q

Routes of entry into the body

A
Inhalation
Gastrointestinal Tract
Contact with mucosa  (Nose
Mouth  Urogenital tract)
Breaks in skin
Eyes
Before, during or after childbirth
52
Q

Examples of Enteric Viruses

A

Picornaviruses (Polio, Enteroviruses, Coxsackievirus) Enteric Adenoviruses
Reoviruses - rotaviruses
Enteric Coronaviruses
HAV - Hepatitis A Virus - (causes acute disease)

53
Q

Enteric Viruses

A

Area of infection: GI

Transmission:

  • Eating and drinking
  • Fecal-oral route: bad sanitation, unwashed hand to mouth contact
  • High surface area of Small Intestines

Type of Viruses: Naked mainly - although coronaviruses are enveloped

54
Q

Urogenital Tract - Sexually Transmitted Viruses

A

Vagina protected by mucous, low pH

Small abrasions (such as from sex), or lesions from other infections, allow viruses to enter past the mucosal layer.

55
Q

Examples of Sexually Transmitted Viruses

A
Herpes Simplex Virus Type 2 (HSV-2)  (HSV-1 through oral-genital contact)
HPV - Human Papillomaviruses 
HIV - also via blood
HBV - also via blood
HCV - also via blood
56
Q

Skin Viruses

A

Dead layer of epidermis is physical barrier, cannot be infected
Infection must occur through abrasions, cuts, bites, needle punctures Infection of epidermis leads to localized infection - no blood or
lymphatics to carry virus to rest of body

Dermis and sub-dermal tissues are highly vascularized

57
Q

Examples of Skin Viruses

A

Papillomaviruses that cause skin warts - localized to basal cells
Rabies virus - bites through skin - virus replicates in neurons Vector borne (mosquitos):
Yellow fever virus
Dengue virus
Zika

58
Q

Eye Viruses

A

Sclera and conjunctiva routes of entry Blinking washes conjunctiva
Injury, abrasions allow viruses to enter Conjunctivitis: localized eye infection
HSV-1 can infect cornea, resulting in blindness, spread to sensory ganglia - ocular herpes

Examples include HSV, Adenoviruses, CMV

59
Q

Neurotropic viruses

A

Herpesviruses replicate in neurons and other cells as well.

Poliovirus enters and replicates mainly in the alimentary tract but can enter motor neurons and cause paralysis

Rabies spreads only via neurons.

Some viruses cross the blood brain barrier via infected macrophages They don’t infect neurons, but can cause neurologic problems
HIV
CMV - Cytomegalovirus
can enter the brain in immunocompromised people These are not strictly “neurotropic”

60
Q

Examples of Neurotropic Viruses

A

Herpes Simplex Viruses (HSV-1, HSV-2)

aricella zoster virus (VZV)
(a.k.a. herpes zoster virus, chickenpox virus)

Poliovirus - it’s primarily a GI infection but can reach the CNS in ~1% of cases

Rabies virus

61
Q

Perinatal Infections

A

Transplacental
CMV (cytomegalovirus)
Rubella virus - can cause congenital rubella syndrome - deafness, heart, eye problems
Zika

At time of birth  
HBV
HCV
Herpes Simplex Virus Type 2 (HSV-2)  HIV
Papillomavirus

So give the mother antivirals prior to birth for HBV, HCV, HSV-2, HIV

Breast Feeding
HIV
CMV

62
Q

Blood for transfusions is tested for which viruses?

A

HIV-1, HIV-2
HBV HCV
HTLV-1, HTLV-2
West Nile Virus

63
Q

TORCH Syndrome

A

Vertically transmitted agents, transplacental or perinatal:
T – Toxoplasmosis / Toxoplasma gondii
O – Other infections
R – Rubella
C – Cytomegalovirus
H – Herpes simplex virus 2 / neonatal herpes simplex

64
Q

Typical Progression of Viral Replication and Disease

A

Barriers to infection

Entry into body
Initial replication at or near site of infection
if virus spreads, this causes primary viremia

Innate immune response

Replication in target tissue, inducing signs of disease and secondary viremia

Spread to other tissues and production of virus that can escape the host

Adaptive immune response

Resolution, or establishment of persistent infection/chronic disease

65
Q

Incubation period

A

from initial infection to overt disease or the ability to detect the virus

66
Q

Virulence

A

The relative degree to which an organism causes disease

Basically the two components of virulence:

  1. How much can it spread
  2. How much can it cause disease
67
Q

what are the components of a virus that cause virulence?

A
  • Virus replication efficiency: how fast, how many new virions are generated
  • Virus effects on cells: death or interference in normal functions
    immune responses
  • Viral spread: how efficiently does the virus infect cells and new hosts
68
Q

Viruses cause disease by

A

Cytopathic effects on infected tissues

Inducing Immune responses that cause symptoms.

Indirect effects that may be less understood. e.g. HIV causes generalized immune activation via poorly understood mechanisms and this results in long term damage to the immune system.

69
Q

Pathogenesis influenced by the infected individual

A

Age

Nutrition

Immune health

Prior immunity

Other underlying pathologies

Genetics - e.g. MHC alleles

70
Q

Mechanisms of how the virus kills the cell

A

Toxic viral components - adenovirus fibers, some HIV proteins. Production of large amounts of viral proteins can disrupt functions of organelles even if the proteins are not “intentionally” toxic.

Inhibition of cellular macromolecular synthesis - many viruses do this.
Herpes simplex viruses inhibit cellular DNA and mRNA synthesis, degrade cell RNA. Poliovirus inhibits cellular protein synthesis.

Syncytia - Herpes simplex, varicella zoster virus. HIV?
This is the fusion of cells caused by the virus spikes being expressed on the surface of infected cells coming into contact with the virus receptors on uninfected cells and causing fusion between the cells (instead of fusion between virus and cell).

Bystander killing: HIV envelope glycoprotein binds to CD4 on uninfected cells and induces them to undergo apoptosis.

Triggering cell suicide - cell’s have sensors to detect invading nucleic acid of viral genomes - dsRNA, cytoplasmic DNA, and then kill themselves via apoptosis or other programmed cell death mechanism.