Big Three Viruses:

• Coronavirus

• Respiratory Syncytial Virus (RSV)

• Influenza Virus (Flu)

Viruses compared to Bacteria:

• Viruses are intracellular obligate parasites

• does not contain a plasma membrane

• does not go through binary fission

• passes through bacteriological filters

• Either DNA or RNA compared to having both

• have no metabolism

• cannot carry protein synthesis

• not sensitive antibiotics

• sensitive to interferon

Discovery of Viruses

There was an infectious agent infecting tobacco plants; Ivanovsky & Beijerninck studied these plants and how the infective agent affected the plants; took the diseased plant leaves and crushed them up; made an extract to filter it and trap the infective agent with the filter; However, they found that the infective agent was so small that it was able to pass through the filter.

• A few years later, with the invention of the electron microscope, they were able to finally see the tobacco mosaic virus that was causing the disease in the tobacco

Virions - complete, infectious forms of a virus outside a host cell. They are essentially the "viral particles" that are capable of infecting a new host. A virus must infect host cells and exploit them to form new virions

Cell types in all taxonomic domains are susceptible to virus infection

Viruses are ubiquitous and are ecologically important

• control populations

Viruses - acellular, obligate intracellular parasites

• All viruses consist of nucleic acid (DNA/RNA) in a protein shell, a capsid, comprised of capsomere units.

  • Must infect a host cell to reproduce; cannot self-replicate

  • Subverts the cell’s machinery and directs it to produce viral particles

Virus Life Cycle:

Virus → host recognition

• through peripheral proteins, glycoproteins on the virus surface or the host cell surface

• No recognition of host means that the virus won’t infect

Takes/uses from the host:

• DNA Polymerase*

• RNA polymerase*

• Ribosomes

• tRNAs

• Nucleotides

• Others: viruses lack a metabolism so they rely on the host.

*Varies on virus and what genome (DNA/RNA) they have

Viral genome enters → Make copies of genome (May integrate into host chromosome before making copies of genome) → transcribe and translate viral genes → create viral proteins → assemble virions (can happen after making copies of genome without transcribing and translating genes and creating preotins) → virus exits

Virus Structure

Acellular; requires host cell; no metabolism

Capsid structure - encloses the viral genome; can vary in shape and size; helical or polyhedral

Genome - single or double stranded DNA or RNA

Enveloped vs naked virus:

• Naked viruses don’t have an envelope around their capsid

• Some animal viruses have an envelope surrounding their capsid (derived from the host plasma membrane as the virus exits the host)

• Envelope may also contain virus specific proteins, including glycoprotein spikes (may also be present in naked viruses).

  • Function in host recognition & attachment

Complex viruses - have complicated structures; possess non-capsid protein components

• EX: bacterial virus (bacteriophage)

Viral infectivity - the virus being successful and being able to replicate itself

• Depends on virus:host recognition

• Interaction between viral surface proteins and host cell surface molecules

Host Range:

• How many different hosts can a virus infect (broad vs. narrow range)

  • Broad → rabies; can infect all kinds of animals

  • narrow → HIV infects only humans

• Animal viruses also exhibit tissue specificity

  • How many different cell types can a virus infect in a host

    • EX: nerve cells, T helper cells (HIV)

Viral Genomes

• Small viruses: genomes encoding < ten genes

• Large viruses: > 100 genes

Viral genes - code for structural components, enzymes used in life cycle (viral genome replication/processing)

• Codes for viral specific genes like capsid proteins, enzymes used in life cycle, etc.

Genome of Zika virus:

• Enveloped virus

• Non-segmented, sing-stranded (+) RNA genome

• 10,794 nt bases long

Genome of Coronavirus

• Envelope virus

• single stranded RNA virus (+)

Influenza virus genome

• segmented, single-stranded (-) RNA genome; 8 segments

• 11 proteins encoded

• 13,500 nt bases total

• Because of the segmented genome, they can recombine (DNA recombination)

For a virus to become infective to humans, they must have contact with humans

The viral life cycle is termed by what genome it has; what can the genome be used for.

Genome of a DNA virus:

• can serve as a template for transcription

• can serve as a template for DNA synthesis

Genome of an RNA virus:

• can serve as a template for translation → (+) RNA viruses (+ refers to the coding strand or the Sense strand)

• Can serve as a template for mRNA synthesis → (-) RNA viruses (- refers to the template strand or the antisense strand. )

• Can serve as a template for DNA synthesis → retrovirus

  • RNA genome is used as a template to create DNA which is then copied back into RNA to create protein

  • A counter to how info flows in every other living thing

(Ask why it does this)

Taxonomy - a viral species is a group of viruses sharing the same genetic information and host range

• classify based on genome type and presence or absence of an envelope

• double-stranded, single-stranded, envelope or no envelope, DNA or RNA, etc.

Viral life cycles

All viral life cycles comprise these events:

• Host recognition & attachment - via recognition/binding of viral capsid proteins, envelope proteins, or glycoproteins to host cell surface proteins and/or glycoproteins

• Genome entry - the entire capsid + genome enters host cell or only the genome may enter

• Synthesis & virion assembly - genome replication, protein synthesis; assembly of virions

• Exit & transmission - release from host cell → progeny infect more host cells

Bacteriophage life cycle

• Lytic cycle - T even phages; are virulent

  • Phage quickly replicates killing host cell (lytic burst)

• Lysogenic cycle - lambda phage; are temperate phages (dormant but can initiate a lytic cycle at some point)

  • does not kill the host immediately

  • Integrates into cell chromosome as a prophage; doesn’t affect the host and host can grow as it normally would; environmental stressors can then trigger the process of lytic cycle

• can be reactive to become lytic

• environmental cues dictate when lysogeny converts to the lytic cycle

Lytic cycle of phage T4

• 1: attachment

• 2: penetration - viral nucleic acid entering cell → degradation of host DNA

• 3: Biosynthesis - where translation occurs; viral DNA and viral proteins produced

• 4: maturation - assembling viral particles; viral particles are “maturing”

  • Eclipse period - the period where the genome enters and begins direct synthesis of viral components and assemble them together

    • occurs up to the point until there’s intact viral particles present

    • represents the steps prior to the complete formation of viral particles

• 5: Release - lysis of host cell wall by lysozyme

Can be up to 100-500 phage per cells

The Lysogenic cycle of Phage

Lambda phages - a type of virus that can integrate its chromosome into the host chromosome

Attachment → penetration → integrates into the host chromosome → creates a prophage → bacterial cell divides w'/ host DNA + prophage replicate → all progeny cells contain prophage → environmental cues trigger the lytic state

• Lysogenic cells immune to reinfection → a cell containing a prophage is not susceptible to infection by another Lambda virus/phage

• Transduction may result in phage conversion: the host cell may acquire new genes carried by prophage

• Lysogenic cycle → lytic cells

• If a cell is lysogenized then it means its integrated the phage genome into its chromosome and contains a prophage

Lysogenic cycle is where we can see an example of the specialized transduction as the prophage exits the chromosome and cell and takes some of its DNA with it

Lytic cycle is where we can see an example of general transduction when we see the degradation of host DNA. Those particles of that DNA can be packaged into the phage instead of the viral genome.

Animal Virus Life Cycle:

• Animal virus infection begins with attachment, entry, then uncoating

  • Attachment: binds to specific proteins on host surface, sometimes uses glycoproteins receptor sites

  • Entry: fusion (enveloped viruses); receptor-mediated endocytosis

  • Uncoating: where the genome is actually released. Separation of the genome of the internalized virus from its capsid -can occur at the cell membrane or nuclear membrane

Some viruses gain entry by taking advantage of receptor-mediated endocytosis (attaching to specific receptors on the host cells to allow it to enter; Viruses exploit these receptors by mimicking the normal molecules that bind to them, allowing the virus to sneak in.)

Some use entry by membrane fusion - enveloped viruses can fuse their envelope with the host cell surface; not all enveloped viruses do this

• Animal viruses then use ribosomes in the host cytoplasm to form proteins

  • Assembly of new virions (capsid, genome) occurs in the cytoplasm or nucleus

  • Enveloped viruses: envelope proteins are inserted into the plasma membrane or organelle membrane

  • Release of virions from host → via lysis or budding

    • budding is what allows virions to gain that envelope that enveloped viruses have

DNA viruses:

• genome replication occurs in nucleus

  • DNA viruses rely on host DNA polymerase which is found in the nucleus

• Synthesis of viral proteins outside the nucleus

• Entry of viral proteins into nucleus

• Viral assembly in the nucleus

RNA viruses:

• genome replication synthesis of viral proteins and viral assembly; all occur outside the nucleus

The replication cycle of an animal virus depends on the form of its genome

• DNA viruses: utilizes the host replication machinery (DNA polymerase); genome can serve as a template for DNA synthesis and for transcription

• Non-retroviral RNA viruses: possess RNA-dependent RNA-polymerase (RDRP; enzyme that copies RNA to RNA); using RDRP, genome can serve as a template for:

  • translation in (+) ss RNA viruses

    • (-) RNA cannot be directly translated into proteins, therefore must be converted into (+) RNA first to be directly translated

  • synthesis of mRNA in (-) ss RNA viruses

• Retroviruses: possess reverse transcriptase (RT); using reverse transcriptase, genome can serve as a template for DNA synthesis.

  • Retroviruses similarly integrate their DNA into the host chromosome. RT allows it to do this as RNA is copied into DNA

review

(Is the RNA replication opposite to the DNA replication in bacterial cell where the Coding strand is used to translate into mRNA instead of the template strand? Ask prof)

DNA viruses can utilize the host replication machinery

Life cycle:

• Nucleus (uncoating)

  • copy genome

  • transcribe genome

• Outside of the nucleus

  • translate mRNAs

  • synthesize viral proteins

• Return to nucleus

  • viral proteins

  • assemble virions

  • exit nucleus

• Exit cells

(+) RNA viruses life cycle

• + RNA → copied into multiple - RNA strands using RDRP → copied again into + RNA strands using RDRP

• the copies of + RNA strands are packaged into viral particles or translated into viral proteins and then assembled into virions

(-) RNA viruses

• - RNA → create multiple copies of + RNA using RDRP → can be translated into viral proteins and then assemble virions or copied back into -RNA using RDRP → - RNA strands are packaged into viral particles

• + RNA used only to translate into viral proteins to assemble virions, not packaged into viral particles

When considering (-) and (+) RNA viruses, we have to be aware of what’s infecting because + RNA viruses can only package + viral particles while - RNA viruses can only package - viral particles

Retrovirus life cycle

+ RNA → reverse transcriptase into (-) DNA → host DNA polymerase copies it into a (+) double strand DNA → can be copied into RNA using host RNA polymerase → RNA is translated into viral proteins and packaged into viral particles

• Retrovirus replication:

  • An enveloped RNA virus; enters by fusion

    • Has 2 identical (+) RNA strands

    • infects T helper cells of immune system

  • uncoating releases RNA genome & viral enzymes, including reverse transcriptase to copy viral RNA to form dsDNA (double strand)

    • DNA integrates into host genome; forming a provirus (integrase)

    • may remain in a persistent state

    • Provirus may be transcribed into RNA; translated into viral proteins

    • Synthesized glycoproteins insert into host cell membrane; virus assembly & exit by budding

Integrase - enzyme that integrates the viral DNA into the host’s cell genome

• Integrase then "cuts" the host's DNA and "pastes" the viral DNA into the host's genome. This integrated viral DNA, called a provirus, can then be transcribed and replicated along with the host's DNA. This integration allows the virus to persist in the host and produce more virus particles.

The provirus can remain in the chromosome for a long time, replicating the virus in a low rate until it gets to the point where it’s detectable. As the virus keep replicating in these cells, more and more T-helper cells are infected which overwhelms the immune system.

Prions - NOT A VIRUS. are proteins that infect animals; they have NO nucleic acid components

• Cause degenerative brain diseases (mad cow disease); Creutzfield-Jacob disease in humans; scrapie; kuru

• Prions diseases transmitted in food, prepared from infected animals

• They’re just an infectious protein

• converts a normal brain cell glycoprotein, PrP^c, into an infectious form, PrP^sc

PrP^sc molecules accumulate in the brain, forming plaques (cavities)

• Destroys cells and creates spongiform holes

Disease progresses very slowly

Prions are highly resistant to physical/chemical agents

Prions replicate itself by binding onto the normal form of glycoproteins which then cause it to become abnormal

Viroids - NOT VIRUSES. are naked RNA molecules - lack a capsid and infect plants

• replicated by host RNA polymerase

• The RNA does not encode for proteins. It’s the RNA molecule itself that causes the effect

• Some have catalytic ability

The viroid RNA may have a complementary plant mRNA strand. The mRNA strand of the plant may compliment the viroid RNA strand which then bind together → it prevents that mRNA from being translated which prevents it from expressing certain genes

There are no viroids that infect humans

Latent Viral Infections - virus that infects host cell, but does not cause disease; can remain in dormant state for long periods

• Oncogenic viruses, herpesviruses, chicken pox (shingles)

• Immunosuppression or stress can activate virus

Persistent (chronic) viral infections - occur gradually over a long period; typically are fatal if not treated

• viruses are continuously released

• HIV-1, -2, Papilloma virus, Hepatitis B virus

In latent infections, you don’t really feel any symptoms at all. In persistent, the symptoms and sickness grows and builds up.