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Viruses, viroids, and prions

Chapter 13

BIO 220

Fig. 13.1

Characteristics of viruses

• Very, very small (filterable)

• Obligatory intracellular parasite

• They have no ribosomes, so must use host cell machinery to translate viral mRNA into viral proteins

• Do not store or generate ATP, so energy is derived from the host cell

• Parasitize host cell for building materials like amino acids, lipids, and nucleotides

• Without the host cell, viruses can not carry out “life”-sustaining processes

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Host range of virus

• Spectrum of cells virus can invade

• Most viruses can only infect specific types of

cells of only one host species

• Range determined by

– Virus must be able to interact with specific

receptor sites on host cell surface

– Availability within the specific host of cellular

factors necessary for viral multiplication

Viral structure

• Viruses are composed of a nucleic acid surrounded by a protein coat called a capsid

• Some viruses have a lipid/protein/CHO envelope surrounding the capsid

• A virion is a complete, fully developed, infectious viral particle located outside a host cell

Nucleic acids

• Virus can have DNA or RNA

• Nucleic acid can be ds or ss

• Nucleic acid may be a few thousand nucleotides up to 250,000 nucleotides

• Nucleic acid may be circular or linear

• For some viruses, the percentage of nucleic acid in relation to protein is about 1% (influenza), can be up to 50% (certain bacteriophages)

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Capsid

• This is the protein coat covering the viral

nucleic acid

• Protein subunits of capsid are called

capsomeres

• Functions:

– Protection

– Contains attachment sites

– Proteins allow viral

penetration of host cell

Fig. 13.2

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Envelopes

• Nonenveloped viruses lack an envelope

• Enveloped viruses do have an envelope

• Some viral capsids are covered by envelopes which may be made of lipids, proteins, and CHOs

– May be a result of extrusion from host cell

– Viral nucleic acid codes for envelope proteins, other components derived from the host cell

• Some envelopes may be covered in spikes (CHO/protein complexes)

Spikes

• May be means of attachment to host cells

• May be used as a means of identification

Fig. 13.3

Influenza

• HA spikes (hemagglutinin spikes)

– Binds sialic acid on host cell membranes

– Bind to erythrocytes and form cross bridges, resulting

in agglutination

– Targeted by antibodies against the influenza virus

• NA spikes (neuraminidase spikes)

– Enable virus to be released from host cell

– Required for viral replication

– Target of drugs like Tamiflu

• Spikes can be used for identification of subtypes

Influenza classification

• A – infects humans and several types of

animals (i.e. birds, horses, swine)

• B – humans

• C – humans, swine, dogs

• Influenza pandemics are caused by Type A

viruses, which are classified into subtypes

based on the HA and NA spikes

• HA (17 versions), NA (10 versions)

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Viruses are tricky

• Some viruses have evolved mechanisms for

evading antibodies (that were produced in

response to that particular virus)

– Viral genes, including those determining viral

surface proteins, are susceptible to mutation

– The progeny of mutant viruses therefore have

altered surface proteins (slight changes in spikes),

which are not recognized by the antibodies

– Antigenic drift

Antigenic shift

• A major change in the virus that

results in new combinations of

HA and NA proteins

• Can take place when a human or

animal is infected with two

different subtypes of virus

• Reassortment of nucleic acids

can result in a modified virus that

humans do not have immunity to

Viral morphology

Based on capsid architecture

• Helical (rabies, Ebola)

• Polyhedral (adenovirus, poliovirus)

• Enveloped (influenza)

• Complex

– Bacteriophages

Fig. 13.5a

Fig. 13.4a

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Classification of viruses

• Way people imagined they were contracted

• Scientists that discovered them

• Based on disease they produce

• Animal/tissue affinity

• Host range or specificity

• Morphological characteristics

– Type of nucleic acid/enveloped or naked/capsid

size/capsid architecture

How can we grow viruses in the lab to

study them?

For animal viruses . . .

• Grow virus in live animals

• Chicken embryos

• Cell/tissue culture

Bacteriophages

• Much easier to grow in lab

Plaque method

Fig. 13.6Plaque forming units – each plaque corresponds to a single virus

Viral multiplication

• The virion nucleic acid contains only a few genes for viral replication

– Genes for viral structural components

– Genes for enzymes used in viral life cycle (i.e. replicating viral nucleic acid)

– Some virions contain a few preformed enzymes

– Genes are only transcribed and proteins made if virus is in host cell

• Most everything else is supplied by host cell

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Viral one-step growth curve

Fig. 13.10

Bacteriophage multiplication

• The lytic cycle (T-even bacteriophage)

– Ends with the lysis and death of host cell

• The lysogenic cycle (Bacteriophage λ)

– Host cell lives

Virulent phages

• Undergoes the lytic cycle

• The result of the lytic cycle is viral replication

and death of the host cell as mature virions

are released

Phage lysozyme

Degradation host DNA

Viral mRNA transcribed/translated

Phage components synthesized

Lysozyme

Fig. 13.11

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Temperate phages

• Can undergo a lytic or lysogenic cycle, depending on environmental conditions

• In the lysogenic cycle the phage DNA is incorporated into the bacterial chromosome

– Prophage is inactive during this period

• The phage DNA can be excised via induction and then enter the lytic cycle Some phages (temperate phages) may proceed through a lytic cycle, but also have the

ability to incorporate their DNA into the host cell’s DNA to begin a lysogenic cycle.

Prophage

gene

repression

Fig. 13.12

Induction

Consequences of lysogeny

• Lysogenic cells are immune to reinfection by the

same phage

• Phage conversion – host cell may exhibit new

properties, i.e. toxin production

– Corynebacterium diphtheriae, Clostridium botulinum

• Specialized transduction is possible

– When a prophage is excised from its host

chromosome, it can take with it a bit of the adjacent

DNA from the bacterial chromosome

Fig. 13.13

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The type of nucleic acid as well as whether or not the virus has an envelope

will determine the life cycle of an animal virus.

Multiplication of animal viruses

• Attachment

• Entry

• Uncoating

• Biosynthesis of virus

• Maturation and release

Multiplication of animal viruses

• Attachment

– Animal viruses have attachment sites that bind to

receptor sites on host cell PM

• Entry

– Many viruses enter by receptor-mediated

endocytosis

– Fusion (enveloped viruses)

Fig. 13.14

Multiplication of animal viruses

• Uncoating

– This is the step where the capsid is removed from

the viral nucleic acid

• Host lysosomal enzymes

• Enzymes encoded by viral DNA that are

synthesized soon after infection

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Biosynthesis of DNA viruses

• Generally, DNA viruses replicate their DNA in

the host cell nucleus by using viral enzymes

• Capsid synthesis in cytoplasm

• Virion assembly in nucleus

• Virions transported to PM for release

Fig. 13.15

Papovavirus – naked, dsDNA

DNA viruses

• Papovaviridae (naked)

– Human papilloma virus

• Herpesviridae (enveloped)

• Adenoviridae (naked)

• Hepadnaviridae (enveloped)

– Hepatitis B

• Poxviridae (enveloped)

Biosynthesis of RNA viruses

• Virus multiplies in cytoplasm

• Viral RNA codes for RNA-dependent RNA

polymerase, which makes a complementary

copy of RNA

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Fig. 13.17

+RNA virus (ss)

Picornaviridae (poliovirus, enterovirus)

Synthesis of host RNA inhibited

Zika virus

• ss +RNA virus, enveloped

• Member of flaviviridae

• Transmitted by Aedes mosquitos, but sexual transmission is also possible

• Zika fever symptoms include headache, fever, maculopapular rash, and conjunctivitis, but symptoms vary

– Can cause a birth defect called microcephaly

– Can also cause Guillain-Barre syndrome in adults

Detection and treatment

Detection

• PCR (detection of viral RNA)

• Presence of antibodies in serum

Treatment

• None

• Vector control!

– Wolbachia

Fig. 13.17

-RNA virus (ss)

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Fig. 13.17

Biosynthesis of RNA viruses that use DNA

Fig. 13.19

Retroviruses & oncogenic RNA viruses

Original viral RNA degraded

Virus may remain

in a latent state or

may be expressed

HIV

• A retrovirus (Lentivirus)

• Two strands of RNA

• Reverse transcriptase

• Phospholipid envelope

with gp120 spikes

• Spread by dendritic cells

• Activated CD4+ cells are

main target

Fig. 19.13

HIV infection of target T cells

Fig. 19.13

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Infection in CD4+ cells

Fig. 19.14

Infection in APCs

Fig. 19.15

How is HIV able to persist?

• Integrated in host genome as provirus

• Virus may not be released by infected cells

(stored as latent virions in vacuoles)

• Some infected cells become a reservoir for the

virus

• Cell-cell fusion

• Rapid antigenic changes due to reverse

transcriptase activity (high mutation rate)

HIV subtypes

• HIV-1

– Most virulent

– Accounts for 99% of cases

– Related to viruses in western Africa that affect primates

– Further subdivided by letter . . .

• HIV-2

– Related to virus that affects the sooty mangabeys

– Not common outside of Africa

– Patients may be asymptomatic for lengthy periods

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Fig. 19.16

Acquired Immunodeficiency Syndrome

(AIDS)

• Final stage of human immunodeficiency virus

(HIV) infection

• Patients susceptible to infections due to

suppressed immune activity

HIV detection

• ELISA (detection of HIV antibodies)

• Western blots

• Real-time PCR

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HIV transmission

• Blood

• Semen

• Intimate sexual contact

• Breast milk

• Transplacental

• Blood-contaminated needles

• Organ transplants

• Artificial insemination

• Blood transfusion

Drugs that inhibit the HIV life cycle

Fig. 19.18

Maturation and release

• Capsid is assembled

• Nucleocapsid forms

• Naked viruses cause rupture of the host cell

• Enveloped viruses often leave the host cell via

a process called budding

– Envelope proteins are encoded by viral genes and

are inserted in host cell PM

– Envelope forms as virion leaves the host

Budding

Fig. 13.20

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Transformation of normal cells into cancer

cells

• Can be due to viruses

• Cancer-inducing genes (oncogenes) carried by viruses are actually derived from animal cells

• Oncogenes can be activated to abnormal functioning by a variety of factors

• Oncogenic viruses can induce tumor formation

– Virus integrates into host cell DNA and replicates along with the host cell DNA, ultimately transforming host cell

• After being transformed by viruses, tumor cells contain a virus-specific antigen on their cell surface (tumor-specific transplantation antigen (TSTA) or in the nucleus (T antigen)

DNA oncogenic viruses

• Adenoviridae

• Herpesviridae

– Epstein-Barr virus

• Poxviridae

• Papovaviridae

– Human papillomaviruses

• Hepadnaviridae

– Hepatitis B

RNA oncogenic viruses

• Retroviridae

– Leukemia virus

Viruses to treat cancer

• Adenovirus (H101)

• Talimogene laherparepvec (T-VEC)

• Reolysin

• Delta 24 cold virus

• Modified measles

• Modified herpesvirus

• Modified HIV

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Viral infections

• A latent viral infection is one in which the virus

remains quiet or latent within a host cell and

does not produce disease for an extended

period, perhaps years

• Persistent viral infections occur gradually over

an extended period of time

Latent and persistent viral infections

Fig. 13.21

Prions

• Proteinaceous infectious particle

• Cause diseases such as kuru, Creutzfeldt-Jakob

disease, fatal familial insomnia, mad cow

disease, scrapie which are characterized by

spongiform encephalopathies

• Disease is caused by the conversion of a

normal host glycoprotein (PrPC) into an

infectious form (PrPSc)

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Fig. 13.22

Plant viruses and viroids

• Plant viruses are morphologically similar to animal viruses and have similar types of nucleic acids

• Because of the presence of the plant cell walls, viruses typically gain access through wounds or are assisted by other parasites (nematodes, fungi, insects)

• Some plant diseases are caused by viroids, which consist of naked RNA