Virology lecture #1 - What is a virus?

Biology W3310 Virology

Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D.

Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu

Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr

Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr • Prof. Saul Silverstein, Ph.D.

Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr • Prof. Saul Silverstein, Ph.D. - sjs6@columbia.edu

Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr • Prof. Saul Silverstein, Ph.D. - sjs6@columbia.edu • TA: Esther Francisco

Biology W3310 Virology • Prof. Vincent Racaniello, Ph.D. - vrr1@columbia.edu - twitter.com/@profvrr • Prof. Saul Silverstein, Ph.D. - sjs6@columbia.edu • TA: Esther Francisco - ef197@columbia.edu

Biology W3310 Virology

Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html

Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html - Schedule, readings, screencasts

Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html - Schedule, readings, screencasts • Textbook: Principles of Virology, Third Edition, ASM Press

Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html - Schedule, readings, screencasts • Textbook: Principles of Virology, Third Edition, ASM Press • virology blog: www.virology.ws

Biology W3310 Virology • Courseworks or http://microbiology.columbia.edu/ w3310.html - Schedule, readings, screencasts • Textbook: Principles of Virology, Third Edition, ASM Press • virology blog: www.virology.ws • This Week in Virology: www.twiv.tv

All living things survive in a sea of viruses

All living things survive in a sea of viruses • We eat and breathe billions of them regularly

All living things survive in a sea of viruses • We eat and breathe billions of them regularly -breathe 6 liters of air per minute, eat thousands of grams of food and its allied contaminants per day, touch heaven knows what and put our ﬁngers in our eyes and mouths

All living things survive in a sea of viruses • We eat and breathe billions of them regularly -breathe 6 liters of air per minute, eat thousands of grams of food and its allied contaminants per day, touch heaven knows what and put our ﬁngers in our eyes and mouths -every milliliter of seawater has more than a million virus particles

All living things survive in a sea of viruses • We eat and breathe billions of them regularly -breathe 6 liters of air per minute, eat thousands of grams of food and its allied contaminants per day, touch heaven knows what and put our ﬁngers in our eyes and mouths -every milliliter of seawater has more than a million virus particles • We carry viral genomes as part of our own genetic material

All living things survive in a sea of viruses • We eat and breathe billions of them regularly -breathe 6 liters of air per minute, eat thousands of grams of food and its allied contaminants per day, touch heaven knows what and put our ﬁngers in our eyes and mouths -every milliliter of seawater has more than a million virus particles • We carry viral genomes as part of our own genetic material • Viruses infect our pets, domestic food animals, wildlife, plants, insects

All living things survive in a sea of viruses • We eat and breathe billions of them regularly -breathe 6 liters of air per minute, eat thousands of grams of food and its allied contaminants per day, touch heaven knows what and put our ﬁngers in our eyes and mouths -every milliliter of seawater has more than a million virus particles • We carry viral genomes as part of our own genetic material • Viruses infect our pets, domestic food animals, wildlife, plants, insects • Viral infections can cross species barriers, and do so constantly - zoonotic infections

The number of viruses impinging on us is staggering

The number of viruses impinging on us is staggering More than 1030 bacteriophage particles in the world’s water supply!

The number of viruses impinging on us is staggering More than 1030 bacteriophage particles in the world’s water supply! • A bacteriophage particle weighs about a femtogram (10-15 grams)

The number of viruses impinging on us is staggering More than 1030 bacteriophage particles in the world’s water supply! • A bacteriophage particle weighs about a femtogram (10-15 grams) 1030 X 10-15= the biomass on the planet of BACTERIAL VIRUSES ALONE exceeds the biomass of elephants by more than 1000- fold!

The number of viruses impinging on us is staggering More than 1030 bacteriophage particles in the world’s water supply! • A bacteriophage particle weighs about a femtogram (10-15 grams) 1030 X 10-15= the biomass on the planet of BACTERIAL VIRUSES ALONE exceeds the biomass of elephants by more than 1000- fold! •The length of a head to tail line of 1030 phages is more than 200 million light years! (calculation: http://www.phagehunter.org/ 2008/09/how-far-do-those-phages- stretch.html)

Andromeda Galaxy - 2.5 million light years away

•Whales are commonly infected with a tiny virus of the Caliciviridae family

•Whales are commonly infected with a tiny virus of the Caliciviridae family •These whale diarrhea viruses cause rashes, blisters, gastroenteritis in marine mammals

•Whales are commonly infected with a tiny virus of the Caliciviridae family •These whale diarrhea viruses cause rashes, blisters, gastroenteritis in marine mammals •They may infect humans

•Whales are commonly infected with a tiny virus of the Caliciviridae family •These whale diarrhea viruses cause rashes, blisters, gastroenteritis in marine mammals •They may infect humans •Infected whales secrete more than 1013 calciviruses daily!!

There are ~1016 HIV genomes on the planet today

There are ~10 HIV genomes 16 on the planet today With this number of genomes, it is highly probable that HIV genomes exist that are resistant to every one of the antiviral drugs that we have now,

Amazingly, the vast majority of the viruses that infect us have little or no impact on our health

Amazingly, the vast majority of the viruses that infect us have little or no impact on our health We exist because we have a defense system that evolved to ﬁght infections

Amazingly, the vast majority of the viruses that infect us have little or no impact on our health We exist because we have a defense system that evolved to ﬁght infections If our immune system is down (e.g. AIDS, organ transplants), even the most common viral infection can be lethal

How ‘infected’ are we?

How ‘infected’ are we? •Each of you in this room is probably infected with at least 2 of the 9 known herpesviruses:

How ‘infected’ are we? •Each of you in this room is probably infected with at least 2 of the 9 known herpesviruses: •HSV-1, HSV-2, VZV, HCMV, EBV, HHV-6, HHV-7, HHV-8, B virus (the latter is 100% lethal for humans, so you probably haven’t seen this one)

How ‘infected’ are we? •Each of you in this room is probably infected with at least 2 of the 9 known herpesviruses: •HSV-1, HSV-2, VZV, HCMV, EBV, HHV-6, HHV-7, HHV-8, B virus (the latter is 100% lethal for humans, so you probably haven’t seen this one) •Once infected with any of these (except B

Every one of your cells is infected with viruses

Every one of your cells is infected with viruses •Each of you has thousands of copies of old and new retrovirus genomes integrated into your DNA

Every one of your cells is infected with viruses •Each of you has thousands of copies of old and new retrovirus genomes integrated into your DNA •About 8% of your DNA is made up of these ancient genomes

Every one of your cells is infected with viruses •Each of you has thousands of copies of old and new retrovirus genomes integrated into your DNA •About 8% of your DNA is made up of these ancient genomes •You will pass these novel entities on to your children and they will do the same to their offspring

Every one of your cells is infected with viruses •Each of you has thousands of copies of old and new retrovirus genomes integrated into your DNA •About 8% of your DNA is made up of these ancient genomes •You will pass these novel entities on to your children and they will do the same to their offspring •What are these genomes doing there?

You are a reservoir for viruses that have set up residence in your lungs and gastrointestinal tract (plus a few other places)

You are a reservoir for viruses that have set up residence in your lungs and gastrointestinal tract (plus a few other places) •All of us are colonized by a variety of adenoviruses, coronaviruses, and rhinoviruses

You are a reservoir for viruses that have set up residence in your lungs and gastrointestinal tract (plus a few other places) •All of us are colonized by a variety of adenoviruses, coronaviruses, and rhinoviruses •Our guts are loaded with bacteria harboring their own blend of viruses

You are a reservoir for viruses that have set up residence in your lungs and gastrointestinal tract (plus a few other places) •All of us are colonized by a variety of adenoviruses, coronaviruses, and rhinoviruses •Our guts are loaded with bacteria harboring their own blend of viruses •Viruses have been with humans since the beginning of our existence

Viruses are amazing This course will teach you why

•This course is designed to help you see the ‘big picture’ of virology

•This course is designed to help you see the ‘big picture’ of virology •I’ll show you how to think about virology as an integrative discipline, not an isolated collection of viruses, diseases, or genes

•This course is designed to help you see the ‘big picture’ of virology •I’ll show you how to think about virology as an integrative discipline, not an isolated collection of viruses, diseases, or genes •I want you to appreciate the molecular wizardry practiced by an often unpredictable organism that pervades the entire ecosystem

•This course is designed to help you see the ‘big picture’ of virology •I’ll show you how to think about virology as an integrative discipline, not an isolated collection of viruses, diseases, or genes •I want you to appreciate the molecular wizardry practiced by an often unpredictable organism that pervades the entire ecosystem •I want you to learn the fundamentals about these molecular wizards that continue to amaze the informed and frighten those who don’t understand the ﬁrst principles

•Virology requires that you know a little about almost every subject in biology

•Virology requires that you know a little about almost every subject in biology •Virology constantly tests your ability to think and pull information together

•Virology requires that you know a little about almost every subject in biology •Virology constantly tests your ability to think and pull information together •While you must memorize the facts, you cannot memorize the many combinations of facts that deﬁne viruses. You have to think.

•Virology requires that you know a little about almost every subject in biology •Virology constantly tests your ability to think and pull information together •While you must memorize the facts, you cannot memorize the many combinations of facts that deﬁne viruses. You have to think. •The devil and the delight are in the details of learning the strategies and tactics of viruses

One of the reasons kids get bored by science is that too many teachers present it as a fusty* collection of facts for memorization. This is precisely wrong. Science isn’t about facts. It’s about the quest for facts — the scientific method, the process by which we hash through confusing thickets of ignorance. It’s dynamic, argumentative, collaborative, competitive, filled with flashes of crazy excitement and hours of drudgework, and driven by ego: Our desire to be the one who figures it out, at least for now. Clive Thompson, Wired 09.08.08

•Viruses are a signiﬁcant part of the ecosystem, infecting every living thing

•Viruses are a signiﬁcant part of the ecosystem, infecting every living thing •Yet, to the uninitiated, viruses are ‘bad news wrapped in a bit of protein’

•Viruses are a signiﬁcant part of the ecosystem, infecting every living thing •Yet, to the uninitiated, viruses are ‘bad news wrapped in a bit of protein’ •Believe me - viruses do much more than cause disease

The Big Picture: A common strategy, unity in diversity

The Big Picture: A common strategy, unity in diversity The basic thesis of this course is that ALL viruses follow a simple three part general strategy to ensure survival:

The Big Picture: A common strategy, unity in diversity The basic thesis of this course is that ALL viruses follow a simple three part general strategy to ensure survival: 1. All viruses package their genomes inside a particle used for transmission of the genome from host to host

The Big Picture: A common strategy, unity in diversity The basic thesis of this course is that ALL viruses follow a simple three part general strategy to ensure survival: 1. All viruses package their genomes inside a particle used for transmission of the genome from host to host 2. The viral genome contains the information to initiate and complete an infectious cycle within a susceptible and permissive cell

The Big Picture: A common strategy, unity in diversity The basic thesis of this course is that ALL viruses follow a simple three part general strategy to ensure survival: 1. All viruses package their genomes inside a particle used for transmission of the genome from host to host 2. The viral genome contains the information to initiate and complete an infectious cycle within a susceptible and permissive cell 3. All viral genomes are able to establish themselves in a host population so that viral survival is ensured

Why study virology if this is all there is to it?

Why study virology if this is all there is to it? • Despite this simple 3-part strategy, the tactics used to achieve it are incredibly diverse

Why study virology if this is all there is to it? • Despite this simple 3-part strategy, the tactics used to achieve it are incredibly diverse • There are countless virus particles out there with amazing diversity:

Why study virology if this is all there is to it? • Despite this simple 3-part strategy, the tactics used to achieve it are incredibly diverse • There are countless virus particles out there with amazing diversity: - size, nature and topology of genomes

Why study virology if this is all there is to it? • Despite this simple 3-part strategy, the tactics used to achieve it are incredibly diverse • There are countless virus particles out there with amazing diversity: - size, nature and topology of genomes - strange particles

Why study virology if this is all there is to it? • Despite this simple 3-part strategy, the tactics used to achieve it are incredibly diverse • There are countless virus particles out there with amazing diversity: - size, nature and topology of genomes - strange particles - unbelievable coding strategies

Why study virology if this is all there is to it? • Despite this simple 3-part strategy, the tactics used to achieve it are incredibly diverse • There are countless virus particles out there with amazing diversity: - size, nature and topology of genomes - strange particles - unbelievable coding strategies - amazing tissue/cell tropism

Why study virology if this is all there is to it? • Despite this simple 3-part strategy, the tactics used to achieve it are incredibly diverse • There are countless virus particles out there with amazing diversity: - size, nature and topology of genomes - strange particles - unbelievable coding strategies - amazing tissue/cell tropism - degrees of pathogenesis from benign to lethal

Nevertheless, there is an underlying simplicity and order to viruses because of two simple

Nevertheless, there is an underlying simplicity and order to viruses because of two simple • All viral genomes are obligate molecular parasites that can only function after they replicate in a cell

Nevertheless, there is an underlying simplicity and order to viruses because of two simple • All viral genomes are obligate molecular parasites that can only function after they replicate in a cell • All viruses must make mRNA that can be translated by host ribosomes: they are all parasites of the host protein synthesis machinery

As viruses are obligate molecular parasites, every solution must reveal something about the host as well as the virus

Be careful: Avoid anthropomorphic analyses

Be careful: Avoid anthropomorphic analyses Viruses do NOT think!

Be careful: Avoid anthropomorphic analyses Viruses do NOT think! (or employ, ensure, exhibit, display, etc...)

Be careful: Avoid anthropomorphic analyses Viruses do NOT think! (or employ, ensure, exhibit, display, etc...) They do not achieve their goals in a human-centered manner

Be careful: Avoid anthropomorphic analyses Viruses do NOT think! (or employ, ensure, exhibit, display, etc...) They do not achieve their goals in a human-centered manner They survive because they make huge numbers of mutants, and selection removes the ill-adapted

Viruses are simple ‘Darwinian Machines’

Viruses are simple ‘Darwinian Machines’ • There is no better model for the concept of ‘survival of the ﬁttest’

Viruses are simple ‘Darwinian Machines’ • There is no better model for the concept of ‘survival of the ﬁttest’ • Think about this a bit more....viruses depend upon their hosts to survive

Viruses are simple ‘Darwinian Machines’ • There is no better model for the concept of ‘survival of the ﬁttest’ • Think about this a bit more....viruses depend upon their hosts to survive • If viruses are too successful and kill their hosts, they may eliminate themselves

Viruses are simple ‘Darwinian Machines’ • There is no better model for the concept of ‘survival of the ﬁttest’ • Think about this a bit more....viruses depend upon their hosts to survive • If viruses are too successful and kill their hosts, they may eliminate themselves • If they are too passive and their hosts’ defenses impede their growth, they may be eliminated

How is the balance of host and virus survival established?

How is the balance of host and virus survival established? The often unexpected twists and turns that lead to virus survival in cells, tissues, organisms, and in a population provide insight into biology and molecular mechanisms not otherwise possible

After this course is over, you will have:

After this course is over, you will have: • Signiﬁcantly better insight into how cells work and interact

After this course is over, you will have: • Signiﬁcantly better insight into how cells work and interact - viruses are a biological ‘wedge’ or ‘hook’ to target complex processes

After this course is over, you will have: • Signiﬁcantly better insight into how cells work and interact - viruses are a biological ‘wedge’ or ‘hook’ to target complex processes • A glimpse of the many ways that information is stored and decoded in genomes

After this course is over, you will have: • Signiﬁcantly better insight into how cells work and interact - viruses are a biological ‘wedge’ or ‘hook’ to target complex processes • A glimpse of the many ways that information is stored and decoded in genomes - how such powerful information can be packed and retrieved from such small viral genomes

After this course is over, you will have: • Signiﬁcantly better insight into how cells work and interact - viruses are a biological ‘wedge’ or ‘hook’ to target complex processes • A glimpse of the many ways that information is stored and decoded in genomes - how such powerful information can be packed and retrieved from such small viral genomes • A basic understanding of viral pathogenesis and infectious disease in general

After this course is over, you will have: • Signiﬁcantly better insight into how cells work and interact - viruses are a biological ‘wedge’ or ‘hook’ to target complex processes • A glimpse of the many ways that information is stored and decoded in genomes - how such powerful information can be packed and retrieved from such small viral genomes • A basic understanding of viral pathogenesis and infectious disease in general - why do you feel so badly when some viruses have their way with you? Immunology actually makes sense when you understand viruses

Assertions you should be able to defend when the course is over

Assertions you should be able to defend when the course is over • Viruses have more biological diversity than all the rest of the bacterial, plant, and animal kingdoms put together

Assertions you should be able to defend when the course is over • Viruses have more biological diversity than all the rest of the bacterial, plant, and animal kingdoms put together • Humans are not at the top of the food chain; the tiny may well inherit the earth

Assertions you should be able to defend when the course is over • Viruses have more biological diversity than all the rest of the bacterial, plant, and animal kingdoms put together • Humans are not at the top of the food chain; the tiny may well inherit the earth • Despite their diminutive size (most viruses have less than 15 genes, some have only 1), viruses excel at survival in a harsh world using sophisticated molecular biology

Assertions you should be able to defend when the course is over • Viruses have more biological diversity than all the rest of the bacterial, plant, and animal kingdoms put together • Humans are not at the top of the food chain; the tiny may well inherit the earth • Despite their diminutive size (most viruses have less than 15 genes, some have only 1), viruses excel at survival in a harsh world using sophisticated molecular biology • Virus-host interactions deﬁne molecular interactions of fundamental and practical signiﬁcance that must be understood if we are to defend ourselves against viruses

• This course will emphasize animal viruses, with some discussion of bacterial viruses

• This course will emphasize animal viruses, with some discussion of bacterial viruses • Many viruses will be ignored simply because of time constraints

How old are viruses?

How old are viruses? • With few exceptions there is no fossil record

How old are viruses? • With few exceptions there is no fossil record • Estimates of molecular evolution place some viruses among the dinosaurs

How old are viruses? • With few exceptions there is no fossil record • Estimates of molecular evolution place some viruses among the dinosaurs • In theory viruses could pre-date cellular life

Ancient references to viral 700 B.C. 1580-1350 B.C.

• Prevention of virus infections in practice since the 11th century without knowledge of agent

• Prevention of virus infections in practice since the 11th century without knowledge of agent • Based on recognition that survivors of smallpox were subsequently protected against disease

• Prevention of virus infections in practice since the 11th century without knowledge of agent • Based on recognition that survivors of smallpox were subsequently protected against disease • Variolation - inoculation of healthy individuals with material from a smallpox pustule (Lady Montagu)

• Prevention of virus infections in practice since the 11th century without knowledge of agent • Based on recognition that survivors of smallpox were subsequently protected against disease • Variolation - inoculation of healthy individuals with material from a smallpox pustule (Lady Montagu) • 1790s - experiments by Edward Jenner in England establish

Concept of microorganisms

Concept of microorganisms • Leeuwenhoek (1632 - 1723) made microscopes, discovered “wee animalcules”, lead to acceptance of microorganisms

Concept of microorganisms • Leeuwenhoek (1632 - 1723) made microscopes, discovered “wee animalcules”, lead to acceptance of microorganisms • Pasteur (1822 - 1895) showed that microorganisms were generated by reproduction, not spontaneous generation

Concept of microorganisms • Leeuwenhoek (1632 - 1723) made microscopes, discovered “wee animalcules”, lead to acceptance of microorganisms • Pasteur (1822 - 1895) showed that microorganisms were generated by reproduction, not spontaneous generation • The Germ Theory of disease, formally enunciated by Koch in

Pasteur’s swan-neck ﬂask http://www.twiv.tv/2009/06/07/twiv-35-much-achoo-about-nothing/

Virus discovery - ﬁlterable agents

Virus discovery - ﬁlterable agents • 1892 - Ivanovsky - found the agent of tobacco mosaic disease passes through ﬁlters that retain bacteria

Virus discovery - filterable agents • 1892 - Ivanovsky - found the agent of tobacco mosaic disease passes through filters that retain bacteria • 1898 - Beijerinck made same finding, but suggested that the pathogen is a distinct agent, not

Virus discovery

Virus discovery • 1898 - Loeffler & Frosch - agent of foot & mouth disease is ﬁlterable

Virus discovery • 1898 - Loeffler & Frosch - agent of foot & mouth disease is ﬁlterable • Key concept: agents not only small, but replicate only in the host, not in broth

Virus discovery • 1898 - Loeffler & Frosch - agent of foot & mouth disease is ﬁlterable • Key concept: agents not only small, but replicate only in the host, not in broth • 0.2 micron ﬁlters (µm, one millionth of a meter)

Virus discovery • 1901 - ﬁrst human virus, yellow fever virus • 1903 - rabies virus • 1906 - variola virus • 1908 - chicken leukemia virus, poliovirus • 1911 - Rous sarcoma virus • 1915 - bacteriophages • 1933 - inﬂuenza virus

Virus From the Latin meaning toxin or poison

Virus From the Latin meaning toxin or poison virion = infectious particle

We know many details about Chemical formula for poliovirus: C332,652 H492,388 N98,245 O131,196 P7,501 S2,340

What is a virus?

What is a virus? • A virus is a very small, infectious, obligate intracellular parasite

What is a virus? • A virus is a very small, infectious, obligate intracellular parasite • Parasite: organism beneﬁts at the expense of the host (a different organism)

What is a virus? • A virus is a very small, infectious, obligate intracellular parasite • Parasite: organism beneﬁts at the expense of the host (a different organism) • Virus particles are not living

What is a virus? • A virus is a very small, infectious, obligate intracellular parasite • Parasite: organism beneﬁts at the expense of the host (a different organism) • Virus particles are not living • Viruses are chemicals, and by themselves cannot reproduce

What is a virus? • A virus is a very small, infectious, obligate intracellular parasite • Parasite: organism beneﬁts at the expense of the host (a different organism) • Virus particles are not living • Viruses are chemicals, and by themselves cannot reproduce • A cellular host is needed for viruses to

Are viruses alive? http://www.virology.ws/2009/11/23/are-viruses-alive/

Viruses are very small Carbon atom ribosome HIV-1 phage TMV poliovirus myosin actin 1,000,000x E. coli 100,000x

How many viruses can ﬁt on the head of a pin? • 500 million rhinoviruses - one of the causes of the common cold • When you sneeze, you ﬁre an aerosol that contains enough viruses to infect thousands

Very small?

Very small? • Mimivirus: largest known virus

Very small? • Mimivirus: largest known virus • host: Amoebae

Very small? • Mimivirus: largest known virus • host: Amoebae • 500 nm particle + 125 nm ﬁbers = 750 nm or 0.75 μm

Very small? • Mimivirus: largest known virus • host: Amoebae • 500 nm particle + 125 nm ﬁbers = 750 nm or 0.75 μm • 1,181,404 bp ds DNA genome encodes 1262 open reading frames

Very small? • Mimivirus: largest known virus • host: Amoebae • 500 nm particle + 125 nm ﬁbers = 750 nm or 0.75 μm • 1,181,404 bp ds DNA genome encodes 1262 open reading frames • Encodes four amino-acyl tRNA synthetases, peptide release factor 1, translation elongation factor EF-TU, translation initiation factor 1, six tRNAs, both type I and type II topoisomerases, components of all DNA repair pathways, many polysaccharide synthesis enzymes

Mimivirus particles can be seen by light microscopy giantvirus.or g

Deﬁning viral attributes

Deﬁning viral attributes • The genome is comprised of either DNA or RNA

Deﬁning viral attributes • The genome is comprised of either DNA or RNA • Within an appropriate host cell, the viral genome directs the synthesis, by cellular systems, of the components needed for replication of the viral genome and its transmission within virus particles

Deﬁning viral attributes • The genome is comprised of either DNA or RNA • Within an appropriate host cell, the viral genome directs the synthesis, by cellular systems, of the components needed for replication of the viral genome and its transmission within virus particles • New virus particles are formed by de novo assembly from newly-synthesized components within the host cell

Deﬁning viral attributes • The genome is comprised of either DNA or RNA • Within an appropriate host cell, the viral genome directs the synthesis, by cellular systems, of the components needed for replication of the viral genome and its transmission within virus particles • New virus particles are formed by de novo assembly from newly-synthesized components within the host cell • The progeny particles are the vehicles for transmission of the viral genome to the next host cell or organism

Deﬁning viral attributes • The genome is comprised of either DNA or RNA • Within an appropriate host cell, the viral genome directs the synthesis, by cellular systems, of the components needed for replication of the viral genome and its transmission within virus particles • New virus particles are formed by de novo assembly from newly-synthesized components within the host cell • The progeny particles are the vehicles for transmission of the viral genome to the next host cell or organism • The particles are then disassembled inside the new cell, initiating the next infectious cycle

A viral infection is an exercise in cell biology Many cell functions required for viral propagation – machinery for translation of viral mRNAs – Energy – enzymes for replication and assembly – transport pathways

Viruses replicate by assembly of pre- formed components into many particles First make the parts, then assemble the ﬁnal product. Not binary ﬁssion like cells

Virus classiﬁcation • Classical hierarchical system: Kingdom Phylum Class Order Family Genus Species

Virus classiﬁcation

Virus classiﬁcation • Viruses are classiﬁed according to four main characteristics:

Virus classiﬁcation • Viruses are classiﬁed according to four main characteristics: - nature of nucleic acid in virion

Virus classiﬁcation • Viruses are classiﬁed according to four main characteristics: - nature of nucleic acid in virion - symmetry of protein shell (capsid)

Virus classiﬁcation • Viruses are classiﬁed according to four main characteristics: - nature of nucleic acid in virion - symmetry of protein shell (capsid) - presence or absence of lipid membrane (envelope)

Virus classiﬁcation • Viruses are classiﬁed according to four main characteristics: - nature of nucleic acid in virion - symmetry of protein shell (capsid) - presence or absence of lipid membrane (envelope) - dimensions of virion & capsid

Virus classiﬁcation • Viruses are classiﬁed according to four main characteristics: - nature of nucleic acid in virion - symmetry of protein shell (capsid) - presence or absence of lipid membrane (envelope) - dimensions of virion & capsid • Genomics has also become

Family: Picornaviridae (picornavirus from ViralZone http://www.expasy.ch/viralzone/

http://

• 40,000 virus isolates from bacteria, plants, animals placed in 3 orders, 73 families, 287 genera, 1950 species. • BUT - there are 106 virions per ml of seawater - most of them unknown!

Viral Genomes BREAKTHROUGH in the 1950s: The viral nucleic acid genome was shown to carry the information needed to replicate, build, and spread virions in the world; it IS the genetic code - seems obvious now, but this discovery in viruses was one of the building blocks of Molecular Biology

Alfred Hershey & Margaret Chase, 1952

Key fact makes life easier for students of virology: Viral genomes must make mRNA that can be read by host ribosomes - all viruses on the planet follow this rule, no exception to date

Key fact makes life easier for students of virology: Viral genomes must make mRNA that can be read by host ribosomes - all viruses on the planet follow this rule, no exception to date Although there are thousands of different virions, there is only a ﬁnite number of viral genomes: There are only SEVEN genome types

David Baltimore (Nobel laureate) used this insight to describe a simple way to think about virus genomes - a major unifying principle in virology

David Baltimore (Nobel laureate) used this insight to describe a simple way to think about virus genomes - a major unifying principle in virology The original Baltimore system missed one genome type: the gapped DNA of the Hepadnaviridae

Deﬁnitions • (+) strand: mRNA, because it can be immediately translated. A strand of DNA of the equivalent polarity is also (+) strand • (-) strand: the complement of the (+) strand; cannot be translated

The elegance of the Baltimore system Knowing only the nature of the viral genome, one can deduce the basic steps that must take place to produce mRNA

The seven classes of viral genomes • dsRNA • dsDNA • ss (+) RNA • gapped dsDNA • ss (-) RNA • ssDNA • ss (+) RNA with DNA intermediate

http://www.polygenicpathways.co.uk	41
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Virology lecture #1 - What is a virus?

by Vincent Racaniello on Feb 08, 2010

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Virology lecture #1 - What is a virus? — Webinar Transcript