Comprehensive Study Notes on Viruses
Viruses
Viruses shape the evolution of organisms.
Lateral gene transfer: 5-8% of the human genome consists of viral genome remnants.
Virtually every system, tissue, and cell in the human body can be infected by at least one kind of virus.
Much research on viruses is motivated by the desire to minimize the damage they can cause.
Epidemics and Pandemics
Viruses have caused some of the most devastating epidemics in recent human history.
Epidemic: Rapidly infects a large number of individuals in a wide area.
Pandemic: A worldwide epidemic.
The “Spanish flu” outbreak of 1918–1919 was the most devastating pandemic to date, killing up to 50 million people worldwide.
Discovery of Viruses
Tobacco mosaic disease stunts the growth of plants and produces mosaic leaf coloration.
Discovered in the late 1800s.
The infectious agent did not share features with bacteria (such as the ability to grow on nutrient media).
The pathogen is now known as tobacco mosaic virus (TMV).
Characteristics of Viruses
Viruses are intracellular parasites that are not cells or organisms.
Cannot manufacture ATP, nucleic acids, or proteins on their own.
Take over a host cell to make copies of themselves.
Each type of virus infects a certain species or cell type.
Genome:
Double- or single-stranded DNA or RNA.
Single linear or circular molecule of the nucleic acid.
Between 3 and 2,000 genes.
Viral Replication
Viruses are obligate intracellular parasites, which means they can replicate only within a host cell.
Host range: Limited number of host species that a virus can infect.
Once a viral genome has entered a cell, the cell begins to manufacture viral proteins.
The virus makes use of host enzymes, ribosomes, tRNAs, amino acids, ATP, and other molecules.
Viral nucleic acid molecules and capsomeres spontaneously self-assemble into new viruses.
Viral Structure
A virus consists of a nucleic acid surrounded by a protein coat.
Capsid: Shell made of protein subunits called capsomeres.
Viral envelopes: Surround capsids of some viruses.
Bacteriophages (phages): Viruses that infect bacteria; the best understood of all viruses.
Phage Reproductive Mechanisms
Phages have two alternative reproductive mechanisms: the lytic cycle and the lysogenic cycle.
Lytic Cycle
Culminates in the death of the host cell.
Produces new phages and lyses (breaks open) the host’s cell wall, releasing the progeny viruses.
A virulent phage reproduces only by the lytic cycle.
Lysogenic Cycle
Replicates the phage genome without destroying the host.
Prophage: Viral DNA incorporated into the host genome.
Temperate phages: Use both the lytic and lysogenic cycles.
Host cell division replicates virus in daughter cells.
Environmental signal → virus genome exits host genome → switch to the lytic mode.
Lambda: Temperate phage widely used in biological research.
CRISPR-Cas System
A bacterial immune system that defends against viruses.
Entering phage DNA triggers transcription of:
CRISPRs: Clustered regularly interspaced short palindromic repeats.
Spacer sequences: Phage DNA inserted between repeats.
Cas proteins: Nucleases, use phage-related RNA to target and cut invading phage DNA.
Animal Viruses
Many animal viruses have an envelope and/or an RNA genome.
Viral glycoproteins on the envelope bind to specific receptor molecules on the surface of a host cell.
The viral envelope is usually derived from the host cell’s plasma membrane as viral capsids exit.
Viral Genetic Material Expression Strategies
Seven strategies exist, all converging on the translation of mRNA.
Class I: dsDNA (DNA viruses)
Class II: ssDNA
Class III: dsRNA
Class IV: (+)ssRNA
Class V: (-)ssRNA
Class VI: (+)ssRNA (RT) (Retroviruses) (DNA to RNA that why it is reverse)
Class VII: dsDNA (RT)
Retroviruses
Reverse transcriptase copies RNA genome into DNA.
Provirus: Viral DNA integrated into host genome, remains a permanent resident of host cell.
RNA polymerase transcribes the proviral DNA into RNA molecules.
The RNA molecules function both as mRNA for synthesis of viral proteins and as genomes for new virus particles released from the cell.
HIV and AIDS
HIV (human immunodeficiency virus): Retrovirus that causes AIDS (acquired immunodeficiency syndrome).
AIDS has killed an estimated 37 million people worldwide.
The highest rates of infection are in east and central Africa.
There are about 34 million HIV-infected people worldwide.
An additional 2.7 million people are infected each year.
Because HIV is primarily a sexually transmitted virus, it disproportionately affects young adults.
Human immunodeficiency virus (HIV) causes acquired immune deficiency syndrome (AIDS).
Destroys immune cells (T cells).
When the T-cell count drops, the immune system’s responses to invading bacteria and viruses become less and less effective.
HIV kills people indirectly—it makes them susceptible to pneumonia, parasites, and unusual types of cancer.
Viral Infection Treatment and Prevention
Viral infections cannot be treated by antibiotics but can be prevented by vaccination.
Vaccine: Non-pathogenic derivative of a pathogen that stimulates the immune system to target the pathogen.
Induces the primary immune response so that the immune system responds quickly and effectively to the pathogen.
Antiviral drugs can help to treat (not cure) viral infections by inhibiting the synthesis of viral DNA and by interfering with viral assembly.
Viral Evolution
As viruses reproduce, mutations occur, generating new strains of a virus.
Memory cells in our immune system will not protect us from new flu strains.
Scientists use a worldwide surveillance system to monitor flu outbreaks and select the three most prevalent strains for use in a single vaccine.
Emerging Viral Diseases
Year of first description | Name | Deaths | Comments |
|---|---|---|---|
1918 | 'Spanish influenza' | In the range of about 50 million | 1918: H1N1; other pandemics in 1957-1958 (H2N2), 1968 (H3N2) and 2009 (H1N1) |
1931 | Rift Valley Fever | Overall CFR <1%; -50% for hemorrhagic fever, Contact with blood or organs of infected animals and mosquito-borne; several outbreaks in 1977, 1997-1998, 2000-2016 | |
1937 | West Nile fever | Mosquito-borne; worldwide outbreaks (most recent 1999-2010, USA) | |
1967 | Marburg hemorrhagic fever | -470; very high CFR | Contact with African green monkey; numerous outbreaks in Africa 1969-2018 |
1969 | Lassa fever | -5,000 deaths annually; CFR | Contact with rodents or contaminated food or items; mostly in West Africa (Nigeria 2018) |
1969 | Acute hemorrhagic conjunctivitis | Rare | First identified in 1969; pandemic in 1981; frequent outbreaks worldwide |
1976-2020 | Ebola hemorrhagic fever | >15,000; CFR | First identified in 1976; first major outbreak in 2013-2016 in West Africa and in 2018 in Democratic Republic of Congo; 29 regional epidemics in 2020 in West and Central Africa |
1981 | HIV/AIDS | -37 million | Ongoing pandemic |
1996 | Avian flu | <1,000?; High CFR | H5N1 and H7N9 viruses from poultry; several outbreaks worldwide; last outbreak in China in 2018 |
1999 | Nipah fever | 813; CFR-10% | Outbreaks in Malaysia, Singapore, Bangladesh and India |
2002 | SARS | 284,000; very high CFR | Contained-did not turn into pandemic |
2009 | H1N1; H7N9 'swine flu' | 935; CFR | Pandemic |
2012 | MERS | Rare | Major outbreak in 2012-2019; ongoing (camels, humans); detected in 27 countries but mostly in Middle Eastern countries |
2014 | Chikungunya | Unknown | Mosquito-borne |
2015 | Zika | >2.3 million; CFR | Mosquito-borne |
2019-ongoing | COVID-19 (SARS-CoV-2) | Pandemic-animal-to-animal, animal-to-human and human-to-human transmission |
Viral Diseases in Plants
More than 2,000 types of viral diseases of plants are known and cause spots on leaves and fruits, stunted growth, and damaged flowers or roots.
Most known plant viruses have an RNA genome.
Many have a helical capsid, while others have an icosahedral capsid.
Plant viruses spread disease by two major routes:
Horizontal transmission, entering through damaged cell walls.
Vertical transmission, inheriting the virus from a parent.
Prions
Infectious proteins that appear to cause degenerative brain diseases in animals (Not a virus).
Scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob disease in humans are all caused by prions.
Like a virus, this is a nonliving pathogen.
Incorrectly folded proteins are able to convert a normal form of a protein into the misfolded version.
Aggregate into a complex that can convert more proteins to prions, which join the chain.
Baltimore Classification of Viruses
The Baltimore classification system is used to classify viruses based on their type of genome and their method of replication.
DNA Viruses
Class I: Double-Stranded DNA (dsDNA) Viruses
Largest group of viruses; 33 families, 142 genera.
Virions are enveloped or naked.
Capsids are icosahedral, complex, or helical.
Genomes are 4.5-2400 kb, as a single circular or linear molecule or multiple linear molecules.
Most infect animals or bacteria; fewer infect protists or archaea.
Not known to infect plants.
Some genera may coexist with the host via lysogeny or latency.
Genome replicated by a semiconservative mechanism.
Genome used as a template for the transcription of mRNA.
mRNA is used to produce viral proteins.
Class II: Single-Stranded DNA (ssDNA) Viruses
9 families, 44 genera.
Most virions are naked; a few are enveloped.
Most capsids are icosahedral; a few are helical.
Genomes are 1.8-12.5 kb, as single or multiple molecules that may be circular or linear.
Most infect animals; fewer infect bacteria or plants.
Marine invertebrates recently identified as hosts.
Genome replicated via a dsDNA intermediate, where either strand is used in progeny virions.
The dsDNA intermediate is used as the template for the transcription of mRNA.
mRNA is used to produce viral proteins.
RNA Viruses
Class III: Double-Stranded RNA (dsRNA) Viruses
12 families, 36 genera.
Most virions are naked; a few are enveloped.
Capsids are icosahedral and often have multiple layers.
Genomes are 3.7-30 kb, as one or more linear molecules.
Animals, plants, and protists are common hosts.
Several are known to infect hosts across different taxa (e.g., animals and plants).
Viral RNA replicase packaged in virion transcribes mRNA from the dsRNA genome.
mRNA is used as a template to make copies of the dsRNA genome.
mRNA is also used to produce viral proteins.
Class IV: Positive-Sense Single-Stranded RNA ((+)ssRNA) Viruses
Largest group of RNA viruses; 32 families, 139 genera.
Virions are enveloped or naked.
Most capsids are icosahedral; a few are helical.
Genomes are 3.4-31 kb, as one or more linear molecules.
Plants and animals are the most common hosts.
Some can infect vertebrates and arthropods (e.g., mosquitoes), which are used as vectors for transmission.
Genomic RNA translated to produce a viral RNA replicase.
The viral replicase makes copies of genomic RNA via dsRNA intermediate.
Copies of the viral genome are used to produce polyproteins, from which viral proteins are generated via cleavage.
Class V: Negative-Sense Single-Stranded RNA ((-)ssRNA) Viruses
9 families, 42 genera.
Most virions are enveloped; a few are naked.
Capsids are helical.
Genomes are 10-25 kb, as one or more linear molecules.
Most infect animals; fewer infect plants.
Not known to infect bacteria or archaea.
Viral RNA replicase packaged in virion transcribes mRNA from the (-)ssRNA genome.
Viral replicase makes copies of (-)ssRNA genomic RNA via dsRNA intermediate.
mRNA is used to produce viral proteins.
Reverse-Transcribing Viruses
Class VI: Reverse-Transcribing (+)ssRNA Viruses
Smallest group of viruses; only 1 family, 8 genera.
Virions are enveloped.
Capsids are icosahedral but may be processed to change shape.
Genomes are 7-11 kb, as a single linear molecule.
Known to infect only humans and other vertebrates.
Viral reverse transcriptase packaged in virion converts RNA genome to dsDNA, which is integrated into the host genome.
Integrated dsDNA is transcribed to replicate the (+)ssRNA genome and produce mRNA.
mRNA is used to produce viral proteins.
Class VII: Reverse-Transcribing dsDNA Viruses
2 families, 9 genera.
Virions are enveloped or naked.
Capsids are icosahedral.
Genomes are 3-8.3 kb, as a single circular molecule, often incomplete dsDNA.
Known to infect only vertebrates and plants.
Genome used as a template.
Viral reverse transcriptase converts (+)ssRNA into dsDNA to replicate the genome.
mRNA is used to produce viral proteins.
Lytic vs. Lysogenic cycles
Lytic Cycle:
Virulent or temperate phage.
Destruction of host DNA.
Production of new phages.
Lysis of host cell causes release of progeny phages.
Lysogenic Cycle:
Temperate phage only.
Genome integrates into bacterial chromosome as prophage, which:
Is replicated and passed on to daughter cells.
Can be induced to leave the chromosome and initiate a lytic cycle.
Dr. Ken Stedman's Research
Focuses on viruses found in the extreme environment of volcanic acid hot springs.
Studying these viruses can help inform viral evolution and the evolution of all life itself.
Dr. Stedman's Courses
Bi 421 Virology: A survey of molecular virology from bacteriophage to SARS-CoV-2 and many viruses in between (Spring, possibly every other year).
Bi 410 Parasitic Diseases: A survey of major human parasitic diseases from Giardia to Malaria with some parasitic worms as well (Spring, possibly every other year).
Bi 431 Advanced Molecular and Cell Biology Research Lab (aka Mutant Viruses from Hell): Course-based Undergraduate Research Experience (CURE), where students learn techniques while working on real research on extreme (non-pathogenic) viruses (Spring). The course is all about the discovery of new mutant viruses.