Viruses

all viruses are parasites

→ most are dependent on the cell’s protein synthesis machinery, ATP, and subunits for its replication

→ they cannot exist outside their host cell as they are dependent on the cell for its replication

→ Parasite: “A parasite is an organism that survives in or on another species, usually at the expense of its host”

viruses are the penultimate parasite

requires eukaryotic or bacterial cells for its replication

viruses are capable of infecting most life on this planet

→includes animals to bacteria

→ each virus is uniquely adapted to its host and generally not capable of infecting member species belonging to a different kingdom

shape and structure of animal viruses

→ helical, icosahedral, ± membrane, equilateral triangle

→ viruses are basically a protein shell (± membrane) encasing nucleic acid (RNA or DNA)

→ capsid (protein shell that protects nucleic acid)

→ envelope = membrane (synonymous)

animal viral genomes

→ either RNA or DNA in nature

→ are classified based on other criteria based on the properties of their genomes

• RNA: + or - strand viral genome; single or segmented, single or double-stranded

• DNA: linear or circular genome

• RNA viral genome that has a DNA intermediate (retrovirus)

adherence

the binding of a microbe to a eukaryotic cell (interaction is very specific)

adhesin

some cell surface proteins present on a microbe that binds a receptor on eukaryotic cells

receptor

some cell surface proteins, glycoproteins, or glycolipids present on eukaryotic cell

tropism

the predilection of a microbe to attach to, invade, or replicate in a particular cell type or tissue

animal viruses

→ infect animals ONLY

→ broad host range: rabies and mammals

→ limited host range: Ebola and primates

bacteriophages

→ infect bacteria ONLY

→ very specific: P22 bacteriophage and salmonella serogroup B. Problem with phage therapy

plant viruses

→ infect plants ONLY

can bacteriophages infect humans?

no

can influenza virus infect the bacterium E coli?

no

capsomere (protein subunit of capsid),

envelop viral protein

spike protein (adenovirus)

all mediate viral attachment to target host cell, binding to some glycolipid or glycoprotein present on the host cell surface

viral replication steps

1) attachment

2) entry/uncoating

3) replication

4) translation

5) assembly

6) release

viruses have adapted to several strategies for entry and uncoating of the viral capsid

some of these mechanisms capitalize on endocytosis and endosome maturation in virally infected cell

binding of some “naked” viruses

causes a conformational change in viral proteins present in the capsid to form a protein channel through which viral nucleic acid passes

envelop viruses

some have proteins that promote the fusion between its envelope and host cell membrane

viral egress

→ naked viruses (no membrane) kill its host cell

→ cell lysis is responsible for the release of infective viral particles

→ viruses directly (proteases) or indirectly (inhibit protein synthesis) disrupt the cytoskeleton (intermediate filaments)

apoptosis

→ programmed cell death

→ activation of caspases, cellular proteases

→ caspases destroy DNAse inhibitor (chromosome fragmentation), degrade cytoskeleton (membrane blebbing), and destruction of Golgi matrix proteins

→ cell membrane changes over to lipid content mostly consisting of phosphatidylserine, a cell surface signal marking the cell for phagocytosis by macrophages

viruses activate apoptosis through:

→ binding to “death” receptors

→ viral nucleic acid activates MAVS which in turn activates caspase-8 and the expression of interferon (IFN). IFN binding to its cognizant receptor also activates apoptosis

→ some viruses inhibit apoptosis (ex. herpesvirus, small pox virus)

→ non-inflammatory

necroptosis

→ swelling organelles, rupture of cell membrane and release of intracellular contents

→ lysis of cells release damage-associated molecular patterns (DAMPS), which alone or in association with PAMPS induced inflammation

innate immunity and inflammation

→ increase vascular permeability at site of infection to allow neutrophil, “natural killer” (NK) cell transmigration

→ chemokines attract neutrophils and NK cells to site of infection

→ activate neutrophils and NK cells for attacking infection

→ “collateral damage” (degransulation): destruction of infected and bystander cells

viral nucleic acid (PAMP)

are recognized by TLR3 which causes that infected cell to produce chemokines and cytokines which results in inflammation at the site of infection