VIRUSES
Chapter 13
VIRUSES
• Latin for poison
• Can infect bacteria, fungi, plants & animals
• 1892 - Iwanoski - tobacco mosaic virus (TMV)
– Filtrate of diseased plant contained infectious material
– Filtrate did not contain bacteria  smaller than bacteria
• 1898 - Beijernick - continued TMV experiments
– Last plant contaminated as severely as the first
– Infectious material is replicating inside plant
GENERAL CHARACTERISTICS
• Obligate intracellular parasites
– Can not replicate outside of host
• Very small (<0.3 m), filterable
– Requires electron microscope to see
• Contain one type of nucleic acid, either DNA or RNA
• Nucleic acid surrounded by a protein coat called the capsid
• Have very little enzymes of their own
– Use host cell enzymes for replication and packaging
– Molecular, nonliving entities (acellular that is not cells)
• May have lipid envelopes
– Susceptible to disinfectants
• Many have a range of host cells able to infect
• Due to specific receptors on cell surfaces
STRUCTURE
•
•
VIRION = complete particle
–
–
Nucleic acid surrounded by capsid +/- lipid envelope
SIZE: 20 - 300 nm (0.02 - 0.3 m)
• Pox virus = largest virus
GENOME: contain a single type of nucleic acid
– Contain either DNA or RNA
– NEVER BOTH RNA and DNA
– Amount varies from a few genes to ~250 genes
•
CLASSIFICATION
– Based on nucleic acid content then
– Capsid
– Envelope
1. NUCLEIC ACID
• DNA or RNA
– Can be single stranded, double stranded, linear or circular; continuous
or segmented
• ssRNA genomes: have a polarity (+ or -)
 + RNA: can go in the cell and directly function as mRNA
 - RNA: must first be transcribed into a +RNA strand which then serves
as the mRNA
• Retrovirus or non-retrovirus
– Retrovirus: RNA transcribed into DNA inside the host
2. CAPSID
• CAPSID: protein coat surrounding the nucleic acid
• Each capsid is composed of units called CAPSOMERS
– May be of one protein of several different proteins
• CAPSID SHAPE or SYMMETRY
– HELICAL
– POLYHEDRAL
– COMPLEX
HELICAL SYMMETRY
• Look like a long rod
• Many copies of the same protein wrapped in a helix
• Nucleic acid surrounded by a hollow, helical, cylindrical capsid
– Tobacco mosaic virus (TMV)
– Rabies virus
POLYHEDRAL SYMMETRY
• Many sides
• ICOSAHEDRAL
– Regular polygon with 20 sides with 12 corners
– Each side = equilateral triangle
• Polio virus
• Adenovirus
• Herpes virus
3. ENVELOPE
• Surrounds the nucleocapsid of some animal viruses
– Enveloped viruses
• Made up of host cell lipids and viral proteins
– Lipid bilayer membrane surrounding the capsid
• May contain viral glycoproteins called PEPLOMERS or SPIKES
– May be used for attachment to host cell
• May help virus get away from the cell
• Keeps segments of a segmented genome together
• Antigenic – host immune system can mount an attack
TAXONOMY of VIRUSES
• AT FIRST: classified by host
– Plant viruses
– Animal viruses
– Bacteriophage
• THEN: classified by disease caused
– Respiratory diseases
– Enteric viruses
• NOW: classified according to structure
– NUCLEIC ACID content
– CAPSID SYMMETRY
– ENVELOPED or NONENVELOPED
VIRAL TAXONOMY
“FAMILY” - viridae
“SPECIES” - group of viruses
Have same nucleic acid and infect same host cells
DNA FAMILIES of VIRUSES #1
• 1. PARVOVIRIDAE
– ssDNA, icosahedral, naked
• Gastroenteritis, fetal death
• 2. ADENOVIRIDAE
– dsDNA, icosahedral, naked
– Respiratory diseases
DNA FAMILIES of VIRUSES #2
• 3. PAPOVAVIRIDAE
–
–
–
–
dsDNA, icosahedral, naked
PA - papilloma = warts
PO - polyoma = tumors
VA - vacuolating = causes vacuoles in host cell
• HPV: human papilloma virus – more than 60 types, benign warts,
plantar warts, laryngeal warts, and cervical warts.
DNA FAMILIES of VIRUSES #3
• 4. POXVIRIDAE
– dsDNA, complex, enveloped
– Largest of all of the viruses
• Smallpox virus – variola, only disease eradicated by vaccination
efforts.
• Cowpox virus - vaccinia
• 5. HEPADNAVIRIDAE
– Circular dsDNA, icosahedral, enveloped
– Unusual replication cycle
• Hepatitis B virus
DNA FAMILIES of VIRUSES #4
• 6. HERPESVIRIDAE
– dsDNA, icosahedral, enveloped
– Very large viruses, become latent
– Ubiquitous in animals
• Large number of these have been discovered
–
–
–
–
Epstein-Barr virus (EBV) - infectious mononucleosis
Cytomegalovirus (CMV)
Varicella-zoster virus (VZV) - chickenpox & shingles
Herpes simplex viruses (HSV)
• HSV-1: fever blisters (oral herpes)
• HSV-2: genital herpes
RNA FAMILIES of VIRUSES #1
•
PICORNAVIRIDAE
 +ve RNA, icosahedral, naked
– PICO = very small
• Polio virus – polio
• Coxsackieviruses
• Enteroviruses (“intestine”)
– Hepatitis A virus (HAV) - acute hepatitis
• Rhinoviruses - common cold
RNA FAMILIES of VIRUSES #2
•
TOGAVIRIDAE

–
–
–
–
+ve RNA, icosahedral, enveloped
TOGA = cloaked or envleoped
Transmitted by arthropods (mosquitoes)
Arboviruses
• Encephalitis viruses
Rubiviruses - respiratory transmission
• Rubella = German measles
RNA FAMILIES of VIRUSES #3
•
•
FLAVIVIRIDAE
 +ve RNA, polyhedral, enveloped
• Flaviviruses – includes Yellow fever
• Hepatitis C virus (HCV)
RETROVIRIDAE
 Diploid +ve RNA*, icosahedral, enveloped
– *Only diploid virus - 2 identical copies of ssRNA
• Each strand ~10kb
– Reverse transcriptase - makes a DNA intermediate to insert into host
chromosome
•
•
•
RNA tumor viruses (oncoviruses)
Leukemia viruses (HTLV-1)
Immunodeficiency viruses (HIV)
RNA FAMILIES of VIRUSES #4
• PARAMYXOVIRIDAE (“near” + “mucus”)
 -ve RNA, helical, enveloped
• Paramyxovirus - parainfluenza
• Mumps virus
• Rubeola virus – measles
• RHABDOVIRIDAE (“rod”)
 -ve RNA, helical, enveloped
– Shaped like bullets with spiked envelope
– Rod with one flat & one curved end
• Rabies virus
RNA FAMILIES of VIRUSES #5
•
ORTHOMYXOVIRIDAE (“straight”)
 Segmented –ve RNA, helical, enveloped
– Influenzaviruses
• Influenza virus A - 1 virus causing disease
– Can infect swine, birds and horses
• Influenza virus B
• Influenza virus C
INFLUENZA VIRUS
• Orthomyxovirus: segmented ssRNA genome
– Has 8 nucleocapsids
– Each contains one ssRNA segment
• Envelope contains 2 different PEPLOMERS
– H = hemagglutinin peplomers
• Attachment to host cell
– N = neuraminidase peplomers
• Helps virus get away from the cell
RNA FAMILIES of VIRUSES #5
•
•
FILOVIRIDAE
 -ve RNA, helical, envleoped
– Long, thread-like
• Ebola virus - hemorrhagic fever - FATAL
• Marburg agent - hemorrhagic fever
BUNYVIRIDAE
 Segmented (3) –ve RNA, helical, enveloped
– Associated with rodents
• Hanta virus - hemorrhagic fever and hantavirus pulmonary
syndrome (HPS)
RNA FAMILIES of VIRUSES #6
•
•
ARENAVIRIDAE
 Segmented (2) -ve RNA, enveloped
• Carried by rodents
• Causes respiratory diseases
• Arenaviruses – Lassa fever
REOVIRIDAE

–
–
–
–
Segmented dsRNA*, icosahedral, naked
*dsRNA = exception
R = Respiratory diseases
E = Enteric diseases
O = Orphan - not associated with any disease
• Rota virus – severe diarrhea in young children
• Colorado tick fever virus
CULTIVATION OF VIRUSES
• Obligate intracellular parasites  depends on the virus and it’s
host cell type
• BACTERIOPHAGE
– Bacteria: suspension or solid media
• PLANT VIRUSES
– Whole plant or plant cell culture
• ANIMAL VIRUSES
– Whole animal, embryonated eggs or animal cell culture
CELL CULTURE
• Most common way of culturing animal viruses
• Three cell lines can be used
– Primary cell lines : derived from tissues by enzymes , generally die
after a couple of generations
– Diploid cell lines: derived from human embryos, multiply for about 50 –
100 generations and then die.
– Continuous cell lines: Immortal lines are derived from transformed or
cancerous cells. Can multiply indefinitely in culture and are immortal.
These are commonly used in propagation of viruses.
VIRAL REPLICATION
• Viral genes code for capsid (structural) proteins and some
enzymes needed for replication
• Virus uses host cell enzymes needed for protein synthesis,
energy production & ribosomes
• Viruses ONLY replicate inside a cell
• Viruses invade host cell and controls metabolic and replicative
“machinery”
– Cell now primarily makes viral proteins and nucleic acid for new viral
particles
VIRUS - HOST INTERACTIONS
•
•
LYTIC CYCLE
–
LYSOGENIC or LATENT CYCLE
–
–
•
Host cell is lysed after viral replication
• T4 bacteriophage
Host cell stays alive after replication
Viral genome is integrated into host’s genome
• Lambda bacteriophage
TRANSFORMING INTERACTION
–
–
–
Viral genome is integrated into host’s genome
Integration alters host cell growth & morphology
Cancer-like cell
THE VIRAL REPLICATIVE CYCLE
•
•
•
•
•
•
•
Attachment or absorption
Penetration
Uncoating
Synthesis
Maturation or assembly
Release
All the steps are similar for DNA and RNA viruses except for
nucleic acid synthesis.
–
Nucleic acid synthesis is different
1. ATTACHMENT OR ABSORPTION
•
Viral particle attaches to host cell via specific receptors on on
the surface of the host cell
–
•
Some proteins and glycoproteins on host cell membranes can function
as receptors for some viruses
Viral particles have attachments sites made of spikes or
fibers that bind these receptors
–
–
Naked viruses - nucleocapsid
Enveloped viruses - envelope
2. PENETRATION
• Entry of viral nucleic acid into host cell
– Can be achieved by endocytosis
– Naked and enveloped can enter this way
• Can be achieved via fusion of envelope with host cell plasma
membrane
– Then viral nucleocapsid enters the cytoplasm
• Uncoating - separation of nucleic acid from the protein capsid
coat
– Can be due to host lysosomal enzymes or configurational changes in the
capsid
3. SYNTHESIS
•
•
Virus takes over host’s biosynthetic “machinery”
–
–
DNA Viruses
–
•
Period of time when new viral nucleic acid molecules, capsid proteins
and other viral components are produced
Synthesis of host DNA & proteins stops
All replicate in nucleus except Poxviruses, uses DNA dependent DNA
polymerase
RNA Viruses
–
All replicate in cytoplasms except retroviruses and orthomyxoviruses,
uses RNA dependent RNA polymerase
4. MATURATION or ASSEMBLY
• Assembly of capsomers into capsid
• Newly synthesized viral DNA is inserted into the newly made
capsids to form new virions
5. RELEASE
•
•
•
•
Naked viruses usually released from host cell by lysing the cell
–
Host cell dies
–
50 - 200 virions are released
–
As they leave the cell, they acquire their envelope from the host cell
plasma membrane
BURST TIME = length of time from attachment to release
BURST SIZE = number of particles released from 1 cell
Enveloped viruses usually bud out of the cell
RETROVIRUSES
• GENOME = RNA
• REPLICATE through DNA intermediate
– Before integrates into host genome must make a dsDNA copy of the
viral RNA genome
• Utilize an enzyme = REVERSE TRANSCRIPTASE
– RNA dependent DNA polymerase
– RNA ------> DNA ----> integrates
RETROVIRAL REPLICATION
• Attachment to host by viral peplomers
• Penetration by fusion with host’s membrane
• Biosynthesis
–
–
–
–
RNA ---> dsDNA
DNA enters nucleus ---> integrates
DNA remains in the host’s genome
Integrated DNA ---> RNA ---> proteins
• Assembly
• Release ---> budding
• RNA ---> DNA ---> RNA
VIRAL LATENCY
• Many viruses can remain latent in the host cell
– Period of time when there is no replication of the viral genome
• No apparent disease occurs during this time
• Virus can be activated by different stimuli
– Now causes disease
• HSV-1
– Remains latent in nerve cells
– Stimulation  cold sores or blisters
• Chicken pox virus
– Remains latent but after activation  shingles
VIRUSES & CANCER
• HTLV - I and HTLV - 2
– Cause cancer in humans
– Human T-cell Lymphotrophic Virus
• Both retroviruses cause leukemia
• Other viruses cause cancer in animals
– EBV : Epstein-Barr virus associated with African Burkitt’s Lymphoma
and nasopharyngeal carcinoma
– HBV: Hepatitis B virus associated with hepatocellular carcinoma ( liver
cancer)
– HPV: human papilloma virus associated with cervical cancer
ONCOGENES
• ONCO = tumor
• ONCOGENE = tumor gene
– Originally derived from normal cellular genes
• ONCOGENIC VIRUS = a virus that promotes tumor formation
• “-OMA” refers to tumor
• SARCOMA VIRUS - promotes tumor formation
PROTOONCOGENES
• Normal cellular genes
– Usually involved in regulating cell growth & division
• Cellular oncogenes = altered or overexpressed protooncogenes
• Both cellular & viral oncogenes promote tumor formation 
cancer
OTHER “CANCER” VIRUSES
• HBV - Hepatitis B virus
– Can cause liver cancer (hepatocellular carcinoma)
– DNA virus - Hepadnaviridae
• EBV - Epstein Barr virus
– African Burkitt’s lymphoma and nasopharyngeal carcinoma
– DNA virus - Herpesviridae
• HPV - Human papilloma virus
– Certain strains associated with cervical cancer
– DNA virus - Papovaviridae
CARCINOGENESIS
• CARCINOGEN = substance that promotes tumor formation
• CARCINOGENESIS = process of tumor formation
• COCARCINOGENESIS - more than one factor is involved in the
formation of tumors
• HBV + excessive alcohol consumption
– Promotes liver cancer?
MECHANISMS of VIRAL DISEASES
•
•
•
•
•
•
•
•
Some promote tumor formation
Some virus lyse the host ---> host cell death
Some break up the host chromosomes
Some stimulate the fusion of several host cells ---->
POLYKARYOCYTE
Some promote changes on cell surface
Some cause shrinking of nucleus
Some stimulate the formation of vacuoles
Some stimulate APOPTOSIS (programmed cell death)
PRIONS
• PROteinaceous INfectious particles
• First identified by Stanley Prusiner in 1982
• DISEASES: kuru, Creuztfeld-Jacob disease, bovine spongiform
encephalopathy (Mad Cow disease), Scrapie (found in sheep)
– All are neurological diseases, spongy appearance of the brain
– All are fatal (slow viral infection)
• INFECTIVE PARTICLE = PROTEIN ONLY
– IS INFECTIOUS
– Goes to the brain
– Converts the normal protein to an infectious protein