Quiz 2: Virology BIOL4090

myxomavirus (MYXV)

a large DNA virus that causes myxomatosis, a severe and often fatal disease in European rabbits

• relative of smallpox

• new world rabbits were the natural host (reservoir), already adapted

• affects european rabbits, not new world rabbits

Frank Fenner

an Australian scientist with a distinguished career in the field of virology. His two greatest achievements are cited as:

1. overseeing the eradication of smallpox, and

2. the attempted control of Australia's rabbit plague through the introduction of Myxoma virus

host

a specific living organism that the pathogen temporarily or permanently inhabits

reservoir

the ecological niche or home base (living or nonliving) essential for the pathogen's survival

pathogenesis

the biological mechanism(s) by which a disease develops and progresses in an affected individual

virulence

a pathogen’s capacity to cause illness or death in an infected host, relative to other isolates or variants of the same pathogen.

what contributes to pathogenesis

viruses and diseases/symptoms

• differentt hings

virus

a tiny, infectious particle made of DNA/RNA that 100% needs a living host cell to make copies of itself

• “obligate intracellular parasites”

• uses hosts to thrive/avoid/adapt in various conditions

• agents of natural selection → changing evolution of host species

germ theory of infectious disease

the scientific principle that specific microscopic organisms called pathogens, or germs, cause infectious diseases

• developed by Louis Pasteur, whom is also credited with originating the foundations of vaccinations (against rabies)

miasma theory

a historical medical belief that diseases like cholera and the plague were caused by a noxious form of "bad air" emanating from rotting organic matter

Koch’s Postulates

four basic rules created in the 19th century by German physician Robert Koch to prove that a specific microbe causes a specific disease

1. First Postulate: The microbe must be present in every single person who is sick with the disease, but it must not be found in healthy people.

2. Second Postulate: The microbe must be taken out of the sick body and grown alone in the lab in a pure culture.

3. Third Postulate: When the cultured microbe is put into a healthy, sensitive host, it must cause the same disease.

4. Fourth Postulate: The same microbe must be taken back out of the newly sick host and proven to be the exact same as the original microbe.

Pasteur-Chamberland FIlter

a porous porcelain water filter invented in 1884 by French microbiologist Charles Chamberland, an assistant to Louis Pasteur.

Tobacco Mosaic Disease

a plant infection that lead to the discovery of viruses

• pasteur-chamberland filter was used multiple times but unsuccessful → virus!

Tobacco Mosaic Virus (TMV)

first viral particle (virion) to be visualized, a cylindrical protein shell built from many copies of a single protein.

Walter Reed

a U.S. Army physician famous for leading the team that proved yellow fever is transmitted by mosquitoes, the first human virus

• saved countless lives

Early Virus Discoveries

1. Existence of infectious agents smaller than bacteria

2. Hosts can be animals, plants, insects, bacteria

3. Causes a wide variety of diseases

4. 100% dependent on host cells to reproduce

Variola virus

a large, double-stranded DNA virus that causes smallpox, a severe and historically devastating human infectious disease.

• highly contagious

variolation

an early historical method used to intentionally infect healthy people with smallpox to create immunity

• Practitioners took scabs or fluid from the sores of a smallpox patient and placed them onto a healthy person.

• inoculation by insufflation

Edward Jenner

An English physician and scientist who pioneered the concept of vaccines and created the smallpox vaccine, the world's first vaccine.

• Noticed that milkmaids who caught cowpox—a mild skin disease from cows—did not catch smallpox.

• The Experiment: In May 1796, Jenner took pus from a cowpox lesion. He inoculated an eight-year-old boy with it.

• The Test: After the boy recovered, Jenner exposed him to the live smallpox virus. The boy did not get sick.

How was smallpox eradicated?

1. Humans only known host

2. Carriers are clearly identifiable and have a short incubation period

3. Surveillance and Ring vaccination

4. Vaccine widely used and generally safe

5. Virus had no host → over

Ring vaccination

a targeted public health strategy used to stop the spread of a disease by vaccinating only the people who had close contact with an infected person, as well as the contacts of those contacts

Viral Reproductive Cycle

1. Attachment

2. Entry

3. Uncoating

4. Genome Replication

5. Gene Expression

6. Assembly/maturation

7. Egress

Attachment Stage

virion binds to the surface of a target cell (e.g, via specific receptors)

Entry Stage

viral genome-containing complex accesses cell interior

Uncoating Stage

a virus removes its protective protein coat, or capsid, to release its viral genome (template) inside a host cell, accessible to polymerases, etc.

Genome Replication Stage

new copies of the viral genome are synthesized

Gene Expression Stage

transcription (RNA) and translation (proteins) of viral genes.

Assembly/Maturation Stage

components (genomes + proteins) from new, infectious virions (viral particles)

• can be spontaneous self-assembly under right conditions, but complex viruses can require cellular energy and other components

Egress Stage

newly formed virions exit from cell

virions

encompass the genome in a protctive shell or protein coating ('“capsid”)

• can be enveloped (have a membrane) or non-enveloped (naked)

• provides the host cell/tissue specificity

• contains other viral factors requred at that time of entry to initiate takeover of the host cell

host cell

a living cell that is infected or invaded by an infectious agent, such as a virus

• viral genomes synthesized in the cell

• mutations occur during viral genome synthesis here

• viral genes expressed in cell.

• provides energy and molecular building blocks (nucleotides, amino acids, membranes) and ribosomes for protein synthesis

Viral genomes

the total genetic material of a virus, made of either DNA or RNA, which is packed inside a protective protein coat called a capsid

• double or single stranded (ssDNA, dsDNA, ssRNA, dsRNA)

• linear or circular (could be both)

• most comprise a single molecule of DNA/RNA, but there are exceptions (segmented & multipartite genomes)

Segmented genomes

genome is split across two or more molecules of DNA or RNA, which get packaged into a single virion

• must incorporate multiple molecules to have a complete genome and be infectious

• true difficulty lies in replication and assembly, making the overall lifecycle of segmented viruses highly inefficient.

Multipartite genomes

genome is split across two or more molecules, each of which is packaged into a separate particle

• the same host cell must be infected with multiple particles to ensure the entire viral genome enters the cell

Packaging signals

specific sequences motifs within a virus's genetic material that direct viral proteins (capsids and coat proteins) to selectively wrap the viral genome instead of host cell molecules

• ensures particles have only viral genome incorporation

cis-acting elements for genome synthesis

specific DNA or RNA sequences on the same molecule that tell the viral replication machinery where/how to replicate the viral genome. (gene expression, replication etc.)

• primer binding sites, polymerase initiation/termination sites

Genes/ORFs

encode virion protein/enzymes, virulence factors

Cis-acting regulatory elements

control the transcription of nearby genes on the same molecule of DNA and control virus gene expression

• promoters, transcription factors, enhancers, terminators

Differences in Viral Genome Sizes

DNA: vary from 1kb → >1000kb

RNA: vary from 7kb → ~30kb

• RNA less stable, therefore can’t adapt and exist as well.

• RNA pol. more error-prone compared to DNA pol.

Are all viruses related?

Unlikely, no evidence pointing to a specific factor (protein, sequence, etc.) common in all viruses

LUCAS

term that refers to “Last Universal Common Ancestor Species” on phylogenetic trees.

Polyphyletic grouping

a collection of organisms that are grouped together based on shared physical traits, but do not share a recent common ancestor

Convergent Evolution

the independent development of similar traits in unrelated or distantly related species

• viruses likely arose multiple times

Three Hypotheses regarding origins of viruses

1. Degenerative cell hypothesis

2. Escaped gene hypothesis

3. Pre-cellular world hypothesis

minimal viral genome components

1. packaging signals

2. cis-acting elements for genome synthesis

3. genes/ORFs

4. cis-acting regulatory elements

Regressive / Degenerate cell hypothesis

a evolutionary theory stating that viruses originated from small, free-living cellular organisms that adopted a parasitic lifestyle and gradually shed their genetic complexity over time.

1. cellular life evolved

2. parasitized other organisms

3. parasite sheds many of its own genomes, a minimal genome remains

4. becomes dependent on hot cell for many functions

5. parasite retains/acquires genes encoding in some sort of capsid

6. packages, copies, reproduce, replicates.

Escaped gene hypothesis

proposes that viruses originated from bits of genetic material like plasmids or transposons that "escaped" from living cells and gained the ability to move between hosts

1. cellular life evolved first

2. A fragment of a genome or a gene in some cellular organism evolved the ability to replicate autonomously

3. progressively gained additional functions, acquiring genes that allowed it coat itsself and exit/enter into other cells.

4. as cellular hosts evolved/diversified, so did the virus and adapted to different kinds of hosts, leading to diversity

Pre-cellular world hypothesis

proposes that self-replicating virus-like genetic elements, like self-replicating nucleic acids, existed before cellular life and contributed to its emergence

1. Pre-cellular “life” began with self-replicating nucleic acids.

2. One of these replicators acquired lipid membranes and became the first “cells” (protocells).”

3. One of these protocells evolved into cellular life forms and eventually gave rise to life as we know it today – bacteria, archaea, eukarya.

4. Viruses also evolved from self-replicating nucleic acids, gaining the ability to parasitize the early protocells/cells and using them to reproduce

5. As cellular life evolved and diversified, viruses adapted and diversified

protocells

self-organized, membrane-bound or membraneless compartments that concentrate biomolecules, serving as the theoretical precursors to living cells in the origin of life