Viruses and what they do -

An overview

Viruses (Encyclopedia Britannica)

..infectious agents of small size and simple composition that can multiply only in living cells of animals, plants and bacteria. Viruses are obligate parasites that are metabolically inert when they are outside their hosts. They all rely, to varying extents, on the metabolic processes of their hosts to reproduce themselves. The viral diseases we see are due to the effects of this interaction between the virus and its host cell (and/or the host’s response to this interaction).

Viruses• Infectious agents of small size and simple composition that can multiply only in living cells of animals, plants and bacteria.

• Viruses are obligate parasites that are metabolically inert when they are outside their hosts.

• The viral diseases we see are due to the effects of this interaction between the virus and its host cell (and/or the host’s response to this interaction).

Viruses are Not Cells

“Smaller” “Bigger”

Virion

capsomeres

Capsid

envelopedvirus

envelope

a Virion

nucleocapsid

Viru

s A

rchi

tect

ure

Minimally, a virus is a proteinaceous carrier of nucleic acid.

Many viruses are more complicated than that, such as having a lipid envelope surrounding the protein capsid.

Viru

s A

rchi

tect

ure

Note spikes projecting from protein capsid surrounding nucleic acid.

Note spikes projecting from lipid envelope-surrounding capsid (which in turn surrounds the nucleic acid).

Some viral shapes

adenovirus

parvovirus

papillomavirus

100 nm1 nm = 1 millionth of a mm100 nm = 1 ten thousandth of a mm

Some viral shapes

herpesvirus

parainfluenzavirus

influenzavirus

poxvirus

1 nm = 1 millionth of a mm100 nm = 1 ten thousandth of a mm

100 nm

Viri

on S

ize`

“Big”

“Medium”

“Small”

“Even Smaller”

Viral Genomes

Nucleic Acid

DNA

RNA

Double Stranded

Positive

Negative

RNA DNA

Single Stranded

Double Stranded

Single Stranded

Vira

l Gen

omes

Nucleic-Acid Virus Genome

ssDNADNA

dsDNA

ssRNA dsDNA ssRNA(the retroviruses)

Negative

Positive

dsRNARNA

ssRNA

One way to distinguish different types of viruses (e.g., influenza virus from HIV) is in terms of the characteristics of their nucleic-acid genomes.

Proteins produced by viruses

• Structural proteins• Non-structural proteins

Term

s D

escr

ibin

g V

irion

s Virion is another name for virus particle. Virions are infectious meaning that they can deliver their nucleic acid to the cytoplasm of a susceptible cell (which for phages would be a bacterium).

Capsid is the the protein coat that surrounds the nucleic acid and defines a virus as a virus.

Capsids are made up of individual proteins called capsomers.

The virion particle consists, minimally, of protein and nucleic acid which together is called a Nucleocapsid.

Many particularly animal viruses have lipid bilayers surrounding the nucleocapsid; those viruses are described as Enveloped.

Non-enveloped viruses are described as Naked. In enveloped viruses the envelope makes initial contact

with cells and subsequent interaction with the cell surface is mediated by envelope proteins (proteins found in or on the envelope lipid bilayer).

Complex (Tailed) Phage VirionNote that this head actually is elongated top to bottom rather than isometric.

Not-Complex Virions

Infection of a cell

Stage Biological implications

Host defenses

Drug intervention

Infection of the animal

• Entry - the beginning of infection– Local replication vs systemic spread

• Consequences of infection– none to illness (signs, symptoms)

• Signs and symptoms• Why some animals get sick while others do not• Patterns of disease

Why do some infected animals get sick and others don’t?

• Viral factors - virulence• Host Factors

Viral Factors:

Why are some isolates of a virus more likely to cause severe disease than

others?determinants of viral virulence

Host Factors:

• Genetic Resistance– loss of receptors

• CCR5-32 mutation and resistance to HIV

– variation in immune response genes– genetic defects in defenses

Host factors:

• age related susceptibility– greater susceptibility of new born animals– greater susceptibility of adults

• prior exposure, acquired resistance• maternal protection• concurrent infections, immuno-suppression, increase

in susceptible cells

Release of virusRelease by lysis of cell(cytopathic)

or by budding (withoutdeath of cell, non-cytopathic)

Incubation period

incubation period - time between infection and the appearance of clinical signs

infection

InterferonsI

II

I

IE

Induced interferongenes

antiviraleffects

activatedfactor

infected cell

ImmuneModulation

Acquired anti-viral immunity (antibody)

BVirus neutralized

Virus infectedcell

Antibody targetsFc receptor bearing cellTo kill virus infected cell

Taxonomy

• What is it?• On what is it based?• Is it important?• Do I need to remember all the details?

International Committee onTaxonomy of Viruses

Groups, types (sero-types), isolates and ‘strains’

Group

Type -A

Type - B

Type - C

Group specific antigen

Type -A specificantigen

Type - C specificantigen

isolate

Group and type specific antigens

group specific antigen

type specific antigen

“naked”virus(eg FMDV)

enveloped virus(eg influenza, FeLV)

Wha

t is

a P

hage

? “The agents were called filterable viruses… Virus

means ‘poison,’ a term that once had been applied to all infectious agents. With time, the adjective filterable was dropped and only the word virus was retained.”

Bacteriophage were originally described as a macroscopic phenomenon that was slightly different from the “poisoning” of a plant or animal.

Instead, what was observed was the destruction of a bacterial culture.

People weren’t all that sure what a bacterium was so the destruction was seen more as an “eating” of the culture (by an otherwise unseen agent) rather than a poisoning.

The filterable agent in this case was described as an “eater” of bacteria, or “Phage” from Greek: Bacteriophage = “Bacteria Eater.”

Wha

t is

a P

hage

? “The agents were called filterable viruses… Virus

means ‘poison,’ a term that once had been applied to all infectious agents. With time, the adjective filterable was dropped and only the word virus was retained.”

Bacteriophage were originally described as a macroscopic phenomenon that was slightly different from the “poisoning” of a plant or animal.

Instead, what was observed was the destruction of a bacterial culture.

People weren’t all that sure what a bacterium was so the destruction was seen more as an “eating” of the culture (by an otherwise unseen agent) rather than a poisoning.

The filterable agent in this case was described as an “eater” of bacteria, or “Phage” from Greek: Bacteriophage = “Bacteria Eater.”

“The word bacteriophage or phage that infect bacteria is both singular and plural when referring to one type of virus. The word phages is used when different types of phages are being referenced.”

Viri

on A

ttach

men

t Org

ans Some virions are isometric: they have a fully symmetrical

capsids, almost spherical.

Isometric virions attach to cells via Attachment Proteins, a.k.a., Spikes which are proteins that symmetrically project from their virions.

Spikes project from capsids in Naked viruses.

Spikes project from envelopes in Enveloped viruses.

Some virions are helical with attachment proteins at end or ends.

Most phages have tailed virions which sort of combine the morphology of isometric and helical virions, with the isometric part called a head and the helical part called a tail.

Attachment is made at the end of the tail opposite the head, and often is mediated by thin “feelers” called tail fibers.

Some Important PhagesHere complex means “tailed”

Note various genome architectures.

An example of Lysogenic Conversion.

Lytic

Infe

ctio

n S

trate

gy

This is the productive-infection strategy followed by most phages including all tailed phages.

Phages that are obligately lytic are called Virulent (vs. chronic or temperate).

Chr

onic

Infe

ctio

n S

trate

gy

This is the strategy followed by filamentous phages.

This is a process called Extrusion.

Late

nt In

fect

ion

Stra

tegy

For phages this is called Lysogeny.

Only Temperate phages are able to display lysogeny.

For phages this is called Lysogenic Conversion.

Vira

l Inf

ectio

n S

trate

gies

Viru

lent

Pha

ge L

ife C

ycle

Chr

onic

Pha

ge L

ife C

ycle

Tem

pera

te P

hage

Life

Cyc

le(s

)

Tem

pera

te P

hage

Life

Cyc

le(s

)

The prophage DNA can remain integrated indefinitely.

This is a process called Induction.

Ads

orpt

ion

& H

ost R

ange

Adsorption describes the virion’s attachment process. The virion contains proteins that recognize molecules

found on the surface of cells (much as antibodies bind to antigens).

Receptor Molecules (typically proteins) are molecules that cells make for various reasons (e.g., transport proteins) which viruses coopt for adsorption.

Typically the Host Range of a virus is determined, at least in part, by the ability of the virus adsorption proteins to bind to host Receptor Molecules.

Restriction-Modification systems can also limit phage host range (as well as biochemical incompatbilities).

Through mutation (and other means) phages can overcome these host-range barriers, resulting, typically in a changed host range.

Because of transduction, these changes in host range can allow gene exchange between even only distantly related bacteria.

Vertebrate RNA Viruses

Vertebrate DNA Viruses

Routes of Transmission

Routes of Transmission

Some viruses are acquired via a respiratory route but cause symptoms elsewhere so aren’t considered “respiratory” viruses; example: measles virus

Ani

mal

Viru

s Li

fe C

ycle Attachment to susceptible cell

Uptake of nucleocapsid into cell

Targeting of nucleocapsid to site of reproduction

Uncoating of nucleic acid from capsid

Synthesis of viral proteins

Replication of nucleic acid

Maturation of virion particles

Virion release from cell

Virus spread within host

Exit of virus from host

Transmission of virus to new host

Ste

ps n

ot s

een

with

Pha

ge Attachment to susceptible cell Uptake of nucleocapsid into cell

Targeting of nucleocapsid to site of reproduction

Uncoating of nucleic acid from capsid

Synthesis of viral proteins

Replication of nucleic acid

Maturation of virion particles

Virion release from cell

Virus spread within host

Exit of virus from host

Transmission of virus to new host

Ent

ry o

f Env

elop

ed V

iruse

s

Note that viral proteins remain on outside of cell and therefore exposed to host immunity.

Ent

ry o

f Env

elop

ed V

iruse

s

Note that viral proteins don’t remain on outside of cell.

Fusion occurs with vesicle membrane rather than plasma membrane

Many Transcription Strategies

Don’t worry about virus names (in red).

Dependence on Host Enzymes

In other words, the greater the size of a virus’ genome, the less dependent that virus is on the host metabolism.

Bud

ding

of E

nvel

oped

Viru

ses

Not all enveloped viruses bud through the plasma membrane.

Note though that naked animal viruses generally lyse their host cell to effect virion release.

Cyt

opat

hic

Effe

ctsCytopathic Effects are changes virus infection makes on host-cell morphologies.

Cells infected with adenovirus.

Cells infected with HSV.

Uninfected cells.

Various Impacts of Animal Viruses on Cells

Impact is virus-type and also host-cell type specific.

Concentrate on the non-tumorgenic aspects of viral infection.

HIV

Life

Cyc

le(th

roug

h re

vers

e tra

nscr

iptio

n)

HIV

Life

Cyc

le(th

roug

h vi

rion

mat

urat

ion)

Note that maturation actually takes place via virion budding!!!

HIV

Life

Cyc

le(b

uddi

ng th

roug

h pl

asm

a m

embr

ane)Reverse transcriptase enzyme already incorporated into capsid.

Tim

e C

ours

e of

Infe

ctio

ns

But note that “the diversity of influenza sequences worldwide in any given year appears to be roughly comparable to the diversity of HIV sequences found within a single individual at one time point.” (Bette Korder as cited in Microbe, 2006 1(3):111-112)H

ow th

e Fl

u C

hang

es it

s “S

pots

”E.g., swapping of coat proteins between avian and human strains of influenza virus.

Particularly important is the protein virus protein, hemagglutinin.

Prion-Associated Disease

These are all Transmissible Spongiform Encephalopathies and all appear to be caused by proteinaceous infectious agents called Prions.

Hyp

othe

sis

for P

rion

Act

ion

Accumulated abnormal proteins kill neuron, with prions spreading to adjacent neurons.

Prevention of infection and/or disease

Protection of the new born animal

antibodies (CMI) in colostrum– maternal immunization– colostrum replacers– implications for immunization of young animals

• caution when using modified-live vaccines• interference by maternal antibodies

Prevention of virus infections/disease

• vaccination– inactivated vaccines– attenuated vaccines– subunit– vectored– DNA vaccines

• management

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Diagnosis of viral diseases

• clinical signs• virus detection• detection of exposure Laboratory}

Detection of virus

Detection of virus

• isolation (isolation +immunological detection)• quantitation (plaque assay, TCID50)• PCR• haemagglutination (or HAI)• ELISA (in clinic or lab)• immunological detection (IH or IF)• electron microscopy

Virus isolation (tissue culture, experimental animals)

cultured cells(two dimensionalanimals) cytopathic effect

immunofluorescence(anti-herpesvirus antibody)

Virus quantitation (plaques)

plaquescount plaques(plaque forming unit/ml)

Haemagglutination (HA)

virus No virus

Enzyme linked immunabsorbant assay (ELISA)

Sample to be tested

virus

capturing antibody

Detecting antibody

Enzyme -> colour

Viruses can be useful too

• biological control of pests• cancer therapy• gene therapy• nanotechnology• symbiotic virus-host relationships

Thank You