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Medical Microbiology > Day 1: Introduction Virology, Virus basics: Entry, replication & exit > Flashcards

Day 1: Introduction Virology, Virus basics: Entry, replication & exit Flashcards

HC01, 02

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1
Q

Viruses and life forms

A

Every life form has own viruses: for bacteria, fungi, plants, animals and some viruses themselves

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2
Q

HepD virus and covirus

A

HepD is a smaller virus which needs other virus to replicate

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3
Q

Is there a kingdom of viruses?

A

No, viruses did not descend from single prehistoric virus

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4
Q

Bacteriophages

A

Viruses that specifically infect bacteria
> most abundant virus in surface water

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5
Q

Virome and detection of it

A

All the viruses in the body or in a certain organ
> detection by high-throughput sequencing

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6
Q

Duration infection with herpesviruses

A

forever

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7
Q

Classification method viruses

A
  • Type of genome: RNA / DNA
    > Symmetry of particle
    > Enveloped or non-enveloped
    > Genome architecture
    » > Single stranded / double stranded
    » segmented or not
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8
Q

Viral capsid use

A

To attach to host cell
> variation in size

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9
Q

Envelope of virus is remaining part of …

A

the host cell membrane

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10
Q

Capsid spikes go through the …

A

envelope (is part of the virus particle itself)

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11
Q

+ and - strands in case ssRNA virus

A

+ strand: like mRNA, directly used for translation
- strand: reverse complement strand, needs to be converted to + strand before translation to make proteins: RNA-dependent RNA polymerase needed (also needed for RNA replication)

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12
Q

Detection envelope for virus?

A

WIth sequencing > easier than electron microscopy

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13
Q

Viruses seem to not live: they are not self-sustained, although they evolve (need host). Name the practical problems with a virus phylogenetic tree

A

All types of genomes exist like ssDNA, dsDNA, (+)ssRNA, (-)ssRNA, dsRNA
> no gene is shared between all viruses

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14
Q

Viral properties (components like molecules)

A

> Made of molecules in living beings: nucleotides, proteins, sugars
can evolve (mutate) and adapt to environment

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15
Q

Viroids

A

RNA viruses
> very small
> without protein coat, plant pathogens

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16
Q

Virusoids

A

Even smaller than viroids
> also called satellites
> circular ssRNA dependent on plant viruses for replication and encapsidation

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17
Q

only known human satellite

A

Hepatitis delta virus (HDV)
> small RNA virus which relies on HBV for encapsidation
> replicates by diverting host DNA dependent RNA polymerases to use RNA as template

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18
Q

Largest known virus

A

Megaviridae family
> linear dsDNA (> 1 Mb)
> largest human infecting virus: herpesvirus

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19
Q

RNA viruses character

A
  • Very large viruses cannot have RNA genome due to instability of large RNA molecules
    > largest RNA viruses infecting humans: coronaviruses
    > also: infidelity of RNA replication
    > higher mutation rate, no proofreading
    > often segmented
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20
Q

Origins viruses: Butterfly vision

A

Virus infection transform cells into virus factories
> maybe cellular phase of the virus is the real life form (virus particles are just the seeds)
> viruses belong to domain of life

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21
Q

Most viruses infect bacteria and plants, but some infect humans. General characteristics:

A
  • Mostly pathogenic
    > interfere with metabolism of the cell and/or invoke a devastating immune response
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22
Q

Smallpox virus

A

Variola virus (VARV) causes smallpox
> genus orthopoxviruses: large viruses as well including VARV and mpox virus

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23
Q

do viruses belong to domain of life?

A

yes

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24
Q

VARV characteristics

A
  • Poxviridae family, genus orthopoxvirus
  • Poxviridae are enveloped unsegmented large dsDNA viruses
    > unlike many dsDNA viruses that replicate in the host, they encode own replication machinery and therefore replicate in cytoplasm
  • human-specific, no animal reservoir
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25
Q

Infection smallpox route

A

After upper respiratory tract infection, virus reaches skin where it replicates to cause widespread vesiculapustular rash, with later scarring especially on face

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26
Q

Two forms of smallpox

A
  • Variola major: serious illness with high mortality rate in unvaccinated population
  • Variola minor: milder infection
    > different strains of VARV
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27
Q

Death from smallpox

A

Secondary to coagulopathy: bleeding because clotting impairment > hypotension and multi-organ failure
> infants, the eldery and pregnant women had the highest fatality rate

28
Q

Complications smallpox

A
  • Keratitis and corneal ulcerations leading to blindness
  • Secondary bacterial skin infections
  • Viral arthritis and osteomyelitis
  • Bacterial pneumonia
  • Orchitis (acute inflammation of testis)
  • Encephalitis
29
Q

VARV eradication

A

First eradicated virus
> Proteins on outside of VARV and cowpox virus are much alike
> vaccine based on horsepox: Vaccinia virus (VACV) replaced the cowpox as smallpox vaccine
> global eradication in 1979
> other orthopoxviruses also exist within family poxviridae

30
Q

Return of smallpox or related virus

A

Mpox
> endemic in DRC (democratic republic of Congo)
> immunologic niches created because vaccinations stopped because of money issues > more susceptibility for the disease in these countries like Australia, Africa and South America

31
Q

Mpox was declared a …. in 2022, which ended in 2023 but returned in 2024

A

PHEIC: Public Health Emergency of International Concern

32
Q

Rabies death source

A

99% human rabies deaths because of dogs infected

33
Q

Novel infectious threats

A
  • Less territory wild animals: increasing number lifestock to feed increasing population
  • More contact
  • Zoonosis risks
  • More international travel: pathogen spread through flying
  • Climate change contributes to pathogen transmission like West Nile Virus in Europe
  • Flying is a great way to disperse pathogens over large distances: plane, bat, bird
34
Q

HC02: Viruses replication and dependency

A

Dependent on host cells to replicate: need cellular machinery to complete replication cycle
> No protein synthesis on themselves: does not code for rRNA and does not contain ribosomal proteins
» do contain some ribosomal protein and tRNA genes to speed up process, but not enough to do it themselves
> need to get into host cell to use cell’s facilities
> sometimes they code for own polymerases

35
Q

The body of the host is well protected against invaders by the largest organ: the skin. How do they enter?

A

Weak points
> Eyes
> Mouth
> Vagina
> Anus
> Scratches/injury
> Placenta: from mother to unborn child

36
Q

Entry into the body: name viruses for the points

A
  • Eyes: Influenza, Rhinovirus
  • Mouth: All respiratory viruses, including influenza virus, norovirus, most herpesviruses
  • Skin: through arthropods bites: dengue virus, through mammalian bites: rabies virus, through injection: HCV, HBV
  • Vagina/Anus: HIV, HSV2, HPV
  • Placenta: HIV, CMV, rubella virus
37
Q

First sign of bird flu

A

The eyes are infected

38
Q

Why cervical cancer when HPV infection

A

Cervix is a barrier and viruses are halted there, mutations and cancer occurs there

39
Q

Rubella virus character

A

Rode hond
> dangerous for fetus specifically, blindness and congenital mistakes early age

40
Q

Difference of cell entry of virus based on:

A

Cell type: bacterial, animal plant cell
> also cell type within species
> Bacteriophages cannot infect human cells

41
Q

How does Ad2 virus enter the cell

A

Clathrin-mediated endocytosis after binding the receptor
> non-oncogenic adenovirus (dsDNA), infects upper respiratory tract

42
Q

Trojan horse strategy of virus cell entry

A

Virus pretends to be something else: nutrient, signal: ligand presentation as pretender)
> Binding ligand by receptor and actively transported in the cell
> like HIV to CD4

43
Q

Virus type and entry mechanism

A

Enveloped: Receptor-mediated endocytosis or direct membrane fusion
Non-enveloped: receptor mediated endocytosis

44
Q

Virus entry: Direct membrane fusion

A

Enveloped viruses
> Envelope with spike proteins was part of the host cell with the original ligand > determines tropism
> Protein interaction induces fusion with the cell membrane: capsid released inside the cell
» cytoplasmic nucleocapsid

45
Q

Virus entry: endocytosis

A

Our cells take up a lot of nutrients and viruses can be engulfed as well
> binds a bit to the cell membrane: endocytosis

46
Q

Envelope of virus

A

Lipid bilayer taken from cell membrane during virus particle budding, through which viral spike proteins protude
> Influenza virus (ssRNA)
> Epstein-Barr virus (dsDNA)

47
Q

Naked viruses

A

Non-enveloped viruses
> do not take lipids from cellular membrane and are often released through cell lysis in culture
> HPV (dsDNA)
> Rotavirus (dsRNA)

48
Q

Entry steps

A
  • Virus binds molecule in cell membrane: can be an unspecific molecule (liek heparan-sulfate or other carbohydrate structures): attachment factors
  • More specific interaction is found afterwards by binding a receptor of the host cell: this interaction initiates conformational changes in virus particle: activate signalling pathways and promote endocytic internalization
49
Q

Herpes simplex virus (HSV) attachment factors

A

Heparan-sulfate on host cell
> then search for stable interaction with receptor
> receptor is the protein which will bind the viral spike proteins in enveloped viruses

50
Q

HIV-1 attachment factors (multiple, used in parallel or succession)

A

Binding of mannose binding C-type lectin receptor family members, the dendritic cell specific adhesion molecule DC-SIGN or L-SIGN (liver/lymph node)

51
Q

HIV-1 receptor binding

A

glycoprotein 120 (gp120) binds CD4 > stable interaction, conformational change > allows virus to associate with co-receptors like CXCR4 and CCR5 chemokine receptors
> membrane fusion

52
Q

Which viral protein binds to the cell membrane protein

A

Enveloped > spike glycoproteins (like gp120 in HIV-1)
Naked > structures that bind receptors are projections or indentations in capsid surface

53
Q

Cellular tropism of virus

A

Determined by specific cellular protein that a virus binds
> if a ubiquitous, a-specific molecule is used > many types of cell, tissue or host can be infected
» HIV-1 cannot infect CD4 negative cells

54
Q

Endocytic pathway used by virus: one or multiple

A

Multiple: because multiple endocytosis systems exist in eukaryotes

55
Q

HCV (hepatitis C virus) entry

A

Endocytosis (enveloped)
- Virion attaches to receptors at cell surface
- Virus-receptor complex is taken into cells by endocytosis
- Membrane fusion in the cell: get envelope out so that contents are released (capsid to cytoplasm)
> route is chosen that binds receptors to activate or inactivate signalling routes so that replication and exit is optimalized.

56
Q

Travel to nucleus

A

For most DNA viruses and some RNA viruses
> replicate in nucleus, need RNA polymerase
> must traverse the nuclear membrane through nuclear pores
> or wait for nuclear membrane to disintegrate during cell division

57
Q

Retrovirus in nucleus or cytosol?

A

Nucleus: pastes DNA into genomic DNA

58
Q

Why can RNA viruses stay in the cytosol?

A

They just need to be translated and maybe converted by own encoded enzymes

59
Q

Cell-to-cell transport of viruses beside budding or exocytosis of virions

A

Mechanisms are created so that no novel attachment of virions to cells is needed:
> cell-to-cell fusion: giant cells (syncytia): virus can move freely in those cells
> after uptake by e.g. macrophages or DCs some viruses can survive degradation in the endosomes and be presented as whole virions to e.g. CD4+ T-cells or between CD4+ T-cells (for HIV-1)

60
Q

Virus replication

A
  • Replication in cytosol or nucleus
    > replication of genome mostly by virus-encoded enzymes
    > transcription (when DNA virus) done by host polymerases (RNAP-2)
    > translation of viral RNA into proteins by host ribosomes
    » viruses can form own subcellular section in the cell for viral replication
61
Q

Exit of virus

A
  • Enveloped viruses: budding: take viral glycoproteins on cell membrane with them: spike proteins
    > Signal peptides present on these glycoproteins to direct them for translocation to cell surface so that they are released with enveloped virus
  • Cell lysis: naked viruses: (only in vitro??, unknown)
  • Vesicles: naked viruses
62
Q

Hep A virus (HAV) characteristics

A
  • Picornavirus: (+) ssRNA
  • 7,5 kb
  • Sole species of genus Hepatovirus
  • Infects via fecal-oral route and is shed in feces as a naked (nonenveloped) particle, but circulates in blood cloaked in an envelope derived from host cell membranes
63
Q

Extracellular vesicles and virus particles

A
  • Extracellular vesicles (like exosomes, microvesicles) are natural lipid particles released by many cell types
    > Exosomes: lipid bilayer extracellular vesicles that are secreted from various cell types and act as mediators of intercellular communication by delivering function proteins, mRNA and miRNA to recipient cells
    » general mechanism to release viral capsids (naked)
64
Q

HEV, poliovirus and rhinovirus all released through

A

Extracellular vesicles
> capsids of HEV particles are individually covered by a lipid membrane that resembles exosome membrane, similar to enveloped viruses (without spikes!), and are released from infected cells via exosomal pathway

65
Q

HEV infection

A
  • (+) ssRNA
  • Orthohepevirus genus of hepeviridae family
  • causive agent of hepatitis E: occurs as waterborne infection in developing countries and zoonotic infection in industrialized countries
66
Q

Exit virus from a host

A

By excretions mainly
> mouth and respiratory system: sneezing, saliva
> GI system: vomit, feces, urine
> Sexual: vaginal epithelium, semen
> Blood: blood sucking insects, needles, cuts
> Organ transplantation, blood transfusion included

67
Q

Survival viruses between hosts

A
  • Difference in eveloped and non-enveloped virions
  • Lipid bilayer of envelope is relatively sensitive to heat and detergents: easy to sterilize, have limited survival outside hosts and normally transfer directly from host to host (like HIV)
    » lose spike proteins, not infectious anymore
  • Non-enveloped viruses: more stable outside hosts: norovirus virions can survive for yeats outside the host

Medical Microbiology (11 decks)

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