General Virology

Viruses

-infectious agents

-intracellular obligate parasites (mult w/in living cells; require host’s metabolic machinery for basic cellular processes)

Virion

infective form of virus outside of the host cell

Viroid

smallest infectious agent (plant), circular ssRNA, no protein coat

Estimate for how many viruses there are

hundreds of millions but only 16,000 have been named

Host range

bacteria, plant, animal (invertebrates, vertebrates); is limited by host receptors

How many species of viruses can infect humans?

200-450

size of viruses

20-400 nm

What are the 3 basic shape of viruses?

Icosahedral, Helical, Complex

Components of a virus

-envelope (not all viruses have this)

-peplomer =spike

-capsid proteins

-genome

Genome of viruses

DNA or RNA (3-100 genes)

*the more genes they have the more complex they are

Capsid

protein coat for protection and binding to receptor; antigenic

Nucleocapsid

capsid w/ enclosed nucleic acid C

Capsomere

-structural subunit of capsid (consists of single or few types of proteins)

-arrangement is characteristic for type of virus

Lipid envelope

only some viruses have this

Naked virus

virus w/out an envelope

Peplomeres (spikes)

-protruding glycoprotein on envelope

-role in receptor binding

-antigenic

Viral Envelope

derived from the host membrane via budding

Virus-encoded glycoproteins (spikes) are synthesized on the

Rough ER membrane

Viruses that are inserted into the ER move via small transport vesicles through

the Golgi complex to the cell plasma membrane

The viral nucleocapsid exits the host cell by budding through the

plasma membrane or by exocytosis

By using the host’s own membrane/proteins the virus can do what?

hide w/in the host cell

Can a virus exit w/ out killing the host

yes

What kind of proteins does the viral envelope have?

-one or more viral envelope proteins

-may contain host proteins

What are enveloped viruses more sensitive to?

-heat

-drying

-alcohols

-detergents

Loss of envelope =

loss of infectivity

Viral Genetics: Types of genome

-DNA or RNA

-ss or ds

-linear or circular

-linear: segmented or non-segmented

Transcription

mode of mRNA (viral (+)RNA) generation

Class I

dsDNA

Class II

ssDNA

Class III

dsRNA

Class IV

(+)ssRNA

Class V

(-)ssRNAC

Class VI

(+)ssRNA-RT

Class VII

dsDNA-RT

Group VI Reverse Transcriptase is

early (envelope independent)

Group VII Reverse Transcriptase is

late (envelope dependent)

Viral life cycle

Attachment→Penetration→Uncoating→Replication→Transcription/Translation→Assembly(maturation)→ release

Attachemnt of viruses

specific binding to receptors on host cell surface (tropism) via glycoproteins in envelope or capsid proteins

Common host receptors

-Sialylated glycans

-Integrins

-Immunoglobulin superfamily members

-Phosphatidylserine receptors

Penetration and Entry: Bacteriophages, some naked animal viruses

viral genome is injected into the host via a pore

Naked animal viruses penetration is done by:

endocytosis

Enveloped animal viruses

fusion of viral membrane and host cell plasma membrane; nucleocapsid is released into cytoplasm; in some cases endocytosis

Uncoating

separation of capsid and nucleic acid

Uncoating: Bacteriophages, some naked animal viruses

capsid is left outside of the host

Uncoating: Naked animal viruses:

vacuole is eventually dissolved; uncoating by host proteases in cytoplasm or for DNA viruses at nuclear membrane

Uncoating: Enveloped animal viruses:

uncoating by host proteases in cytoplasm or for DNA viruses at nuclear membrane

Biosynthesis (genome and capsid components): DNA viruses

replication and transcription in cytoplasm foBiosynthesis (genome and capsid components): r prokaryotic host and nucleus for eukaryotic host

Biosynthesis (genome and capsid components): RNA viruses

replication and transcription usually in cytoplasm although there are exceptions

All protein synthesis occurs where?

cytoplasm

Assembly of the protein capsid around the nucleid acid

-RNA viruses are usually assembled in the cytoplasm

-DNA viruses are assembled in the nucleus

Release: Bacteriophages, naked animal viruses

Lysis of host cell via viral cytolysins (note: some viruses are known for non-lytic dissemination)

Release: Enveloped animal viruses

release via exocytosis; slow disintegration of host cell over time, or elimination by immune cells

How many virions are released

10,000-50,000 (lots)

Acute infection

-short incubation period

-self limiting: recovery or death can happen in short period of time (about 2 weeks)

Persistent infection

viral pathogen is not cleared but remains in infected host (there are 3 categories)

Persistent infection: Chronic

virus is detectable in the body at all times; signs and symptoms may be present or absent for extended period of times

Persistent infection: latent (dormant)

virus remains undetectable until signs reappear can remain latent for months or years w/out causing disease

Reactivation of a virus can be caused by:

stress, sunlight, other viral infections, compromised local immunity

Persistent infection: slow

w/ or w/out initial acute phase; # of viruses slowly increases over long periods of time during which there are no major signs (is often fatal)

Transmission via

-respiratory droplets or aerosols

-contaminated food or water

-Body fluids(blood, saliva, urine, semen) or tissue (transplanted organ)

Direct inoculation (insect bite or contaminated needle)

Enveloped viruses are often transmitted by:

aerosols and body fluids (parenteral route)

Naked viruses are often transmitted via

oral-fecal route

Viruses are spread in the body mainly by

the blood stream and the lymphatic system

Viremia

transport of viruses in the blood

Some viruses can cross the placenta and infect the

fetus

Virulent factors of viral pathogens: attachment

determines host range; tissue tropism

Virulent factors of viral pathogens: Evasion of host defenses

residing inside host cell (latency)

viral proteins: virokines

homologous to cytokine→ immune modulators

viral proteins: viroreceptors

homologous to cytokine and antibody receptors→ molecular mimicry

Tunneling Nanotubes (TNT)

Actin-based intracellular conduits that connect distant cells and allow intercellular transfer of molecular information. Some viruses trigger formation of TNT and use them to spread to uninfected cells

Cell Damage

-causing cell lysis in the final stage of viral life cycle (in order to distract the cell)

-incorporation of viral proteins in host cell membranes leads to cell destruction by immune defense

-transformation of cells into malignant ones (oncogenic viruses; usually DNA viruses; uncontrolled replication)

Antigenic drift

point mutation causes small changes in surface proteins (minor changes over time)

Antigenic shift

recombination causes large changes in surface proteins (major changes → can lead to epidemics or pandemics)