Understanding Viruses

Sahibzada Tasleem Rasool
The students will be able to
a. Define basic structures of viruses.
b. Describe properties of naked and enveloped viruses
c. Discuss the nomenclature and classification of viruses
d. Identify various groups of viruses
e. Describe viral pathogenesis and steps involved in that.
f. Discuss mechanisms of genetic material exchange among viruses.
g. Describe outcomes of genetic variation.
h. Timelines and disease patterns

Introduction to Viruses
A virus is an obligate intracellular parasite and it is
minimally constructed f two elements
• A Genome …… DNA or RNA
• Protein content…..which makes the capsid and
some necessary proteins including enzymes
Viruses could be
• Non-enveloped
• Enveloped

Basic virus structure
Capsid
protein
Nucleocapsid
Naked capsid
virus
DNA
RNA
or =
+
Nucleocapsid
Lipid membrane,
glycoproteins
Enveloped virus
+

Capsid symmetry
Icosahedral Helical
Naked capsid
Enveloped
Lipid
Glycoprotein
Matrix

Icosahedral naked capsid viruses
Adenovirus
Electron micrograph
Foot and mouth disease virus
Crystallographic model
http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Ackerman/Animalvi/Adenovir/799-16.htm
http://virology.wisc.edu/virusworld/ICTV8/fmd-foot-and-mouth-ictv8.jpg

Helical naked capsid viruses
Tobacco mosaic virus
Electron micrograph
Tobacco mosaic virus
Model
RNA Protein
http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/em_tmv.gif
Caspar
and
Klug,
Adv
Virus
Res.
1960;7:225-325

Icosahedral enveloped viruses
Herpes simplex virus
Electron micrograph
Herpes simplex virus
Nucleocapsid cryoEM model
http://web.uct.ac.za/depts/mmi/stannard/emimages.html
http://virology.wisc.edu/virusworld/images/herpescapsid.GIF

Helical enveloped viruses
Influneza A virus
Electron micrograph
Paramyxovirus
Electron micrograph
http://web.uct.ac.za/depts/mmi/stannard/fluvirus.html
http://web.uct.ac.za/depts/mmi/stannard/paramyx.html

Properties of enveloped viruses
 Envelope is sensitive to
 Drying
 Heat
 Detergents
 Acid
 Consequences
 Must stay wet during transmission
 Transmission in large droplets and secretions
 Cannot survive in the gastrointestinal tract
 Do not need to kill cells in order to spread
 May require both a humoral and a cellular immune
response
Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA Box 6-5

Properties of naked capsid viruses
 Capsid is resistant to
 Drying
 Heat
 Detergents
 Acids
 Consequences
 Can survive in the gastrointestinal tract
 Retain infectivity on drying
 Survive well on environmental surfaces
 Spread easily via fomites
 Must kill host cells for release of mature virus particles
 Humoral antibody response may be sufficient to neutralize
infection
Adapted from Murray, P.R. Rosenthal K.S., Pfaller, M.A. (2005) Medical Microbiology, 5th edition, Elsevier Mosby, Philadelphia, PA , Box 6-4

VIRUSES
DNA RNA
Single Stranded Double Stranded
Double Stranded Single Stranded

David Baltimore places viruses in to one of the seven groups depending on a
combination of their nucleic acid (DNA or RNA), strandedness (single-stranded or
double-stranded), and method of replication.
DNA viruses
Group I ……………dsDNA Viruses
Group II ………….. ssDNA Viruses
RNA viruses
Group III …………. dsRNA Viruses
Group IV …………. ssRNA Viruses +ive sense
Group V ……………ssRNA Viruses -ive sense
Reverse transcribing viruses
Group VI…………RNA Reverse Transcribing Viruses
Group VII……….. DNA Reverse Transcribing Viruses

Classification of Human Viruses
"Group" Family Genome Genome size (kb) Capsid Envelope
dsDNA
Poxviridae dsDNA, linear 130 to 375 Ovoid Yes
Herpesviridae dsDNA, linear 125 to 240 Icosahedral Yes
Adenoviridae dsDNA, linear 26 to 45 Icosahedral No
Polyomaviridae dsDNA, circular 5 Icosahedral No
Papillomaviridae dsDNA, circular 7 to 8 Icosahedral No
ssDNA
Anellovirus ssDNA circular 3 to 4 Isometric No
Parvoviradae ssDNA, linear, (- or +/-) 5 Icosahedral No
Retro
Hepadnaviridae dsDNA (partial), circular 3 to 4 Icosahedral Yes
Retroviridae ssRNA (+), diploid 7 to 13 Spherical, rod or cone shaped Yes
dsRNA
Reoviridae dsRNA, segmented 19 to 32 Icosahedral No
ssRNA (-)
Rhabdoviridae ssRNA (-) 11 to 15 Helical Yes
Filoviridae ssRNA (-) 19 Helical Yes
Paramyxoviridae ssRNA (-) 10 to 15 Helical Yes
Orthomyxoviridae ssRNA (-), segmented 10 to 13.6 Helical Yes
Bunyaviridae ssRNA (-, ambi), segmented 11 to 19 Helical Yes
Arenaviridae ssRNA (-, ambi), segmented 11 Circular, nucleosomal Yes
Deltavirus ssRNA (-) circular 2 Spherical Yes
ssRNA (+)
Picornaviridae ssRNA (+) 7 to 9 Icosahedral No
Calciviridae ssRNA (+) 7 to 8 Icosahedral No
Hepevirus ssRNA (+) 7 Icosahedral No
Astroviridae ssRNA (+) 6 to 7 Isometric No
Coronaviridae ssRNA (+) 28 to 31 Helical Yes
Flaviviridae ssRNA (+) 10 to 12 Spherical Yes
Togaviridae ssRNA (+) 11 to 12 Icosahedral Yes

Virus replication: general

Group I:
Viruses possess double-stranded DNA and include such
virus families as Herpes viridae (examples like
• HSV1 (oral herpes),
• HSV2 (genital herpes),
• Vericilla Zoster Virus (chickenpox),
• EBV (Epstein-Barr virus),
• CMV (Cytomegalovirus)),
• Poxviridae (smallpox)

Group II:
Viruses possess single-stranded DNA and include such
virus families as Parvo-viridae (Parvo virus) and the
important bacteriophage M13.

RNA viruses
Group III:
Viruses possess double-stranded RNA
genomes, e.g. rotavirus. These genomes are
always segmented.

Group IV:
Viruses possess positive-sense single-stranded RNA
genomes. Many well known viruses are found in this group,
including the picorna viruses (which is a family of viruses that
includes well-known viruses like
•Hepatitis A virus,
•enteroviruses,
•rhinoviruses,
•poliovirus,
•foot-and-mouth virus),
•SARS virus,
• hepatitis C virus,
•rubella virus.

Group V:
Viruses possess negative-sense single-stranded RNA
genomes. The deadly Ebola and Marburg viruses are well
known members of this group, along with
• influenza virus,
• measles,
• mumps
• rabies.

Group VI:
Viruses possess single-stranded RNA genomes and
replicate using reverse transcriptase. The retroviruses
are included in this group, of which HIV is a member.

.
Group VII:
Viruses possess double-stranded DNA genomes and
replicate using reverse transcriptase. The hepatitis B virus
can be found in this group. See diagram next slide
The replication of the viruses can be better understood
once their classification and nomenclature is clear. The
viruses are classified according to the type of genetic
material they contain.

Viral pathogenesis
 Cycle of infection
 Entry
 Primary site replication
 Spread within the host
 Shedding
 Transmission
 Effects on cells
 Effects on organism

Cycle of infection
Secondary sites
Spread
Entry Shedding
Shedding
Local
Lymphatic
Neuronal
Blood (viremia)
Primary site

Entry
 Mucous membranes or skin
 Respiratory
 Oral
 Sexual
 Ocular
 Percutaneous
 needles, wounds, bites

Shedding, transmission
 Routes
 Respiratory
 Gastrointestinal (oral-fecal)
 Urogenital
 Skin
 Mechanisms
 Indirect contact
 Aerosols
 Fomites
 Direct contact
 Lesions
 Saliva
 Sex
 Animal or insect bites
 Maternal-neonatal

Portals of entry of viruses into the host, and sites of shedding from the host. (From Fields Virology, 4th ed, Knipe & Howley, eds,
Lippincott Williams & Wilkins, 2001, Figure 9-2)
Routes of entry and shedding

Exchange of genetic information between two genomes.
"Classic" recombination
This involves breaking of covalent bonds within the nucleic acid,
exchange of genetic information, and reforming of covalent bonds.
This kind of break/join recombination is common in DNA viruses or
those RNA viruses which have a DNA phase (retroviruses). The
host cell has recombination systems for DNA.
Recombination enables a virus to pick up genetic information from
viruses of the same type and occasionally from unrelated viruses
or even the host genome

DNA virus recombination

If a virus has a segmented genome and if two
variants of that virus infect a single cell, progeny
virions can result with some segments from one
parent, some from the other.
This is an efficient process - but is limited to viruses
with segmented genomes. Reassortment is a non-
classical kind of recombination
Reassortment may play an important role in nature
in generating novel reassortants.

RNA virus reassortment

Clinical significance of genetic variation
 Antigenic variation…..Body can not coup with the virus
 Drug resistance……..Difficulty in designing and making
new vaccines

Time course of infection; host response
prodrome
symptoms at
secondary sites
pro-
drome
symptoms at
primary site
healing
innate immunity:
interferon
adaptive immunity:
cellular, antibody
inflammatory;
immunopathogenesis
0 2 4 6 8 10 12
time (days)
Infection without spread:
Infection with spread:
Host Response:

Patterns of disease
From Schaechter’s Mechanisms of Microbial Disease; 4th ed.; Engleberg, DiRita & Dermody; Lippincott, Williams & Wilkins; 2007; Fig. 31-9

Major diseases caused by human viruses
"Group" Family Human pathogens (disease)
dsDNA
Poxviridae Variola (smallpox); Orf (pustular dermatitis); Molluscum contagiosum (pustular dermatitis)
Herpesviridae Herpes simplex 1,2 (oral, genital herpes); Varicella-zoster (chickenpox); Epstein-Barr (mononucleosis);
Cytomegalovirus (neonatal abnormalities); HHV6 (roseola); HHV8 (Kaposi's sarcoma)
Adenoviridae Adenovirus (respiratory infection, conjunctivitis)
Polyomaviridae Polyomavirus (benign kidney infection, respiratory disease, leukoencephalopathy)
Papillomaviridae Papillomavirus (warts, genital carcinoma)
ssDNA
Anellovirus Unknown
Parvoviradae B-19 (fifth disease, fetal death)
Retro
Hepadnaviridae Hepatitis B ("serum" hepatitis)
Retroviridae HIV (aids); HTLV (leukemia)
dsRNA
Reoviridae Rotavirus (infantile gastroenteritis)
ssRNA (-)
Rhabdoviridae Rabies virus (rabies)
Filoviridae Ebola virus (ebola)
Paramyxoviridae Parainfluenza virus (respiratory infection); Mumps virus (mumps);
Respiratory syncytial virus (respiratory infection); Measles virus (measles)
Orthomyxoviridae Influenza virus (influenza)
Bunyaviridae Hantaan virus (hemorrhagic fever with renal syndrome)
Arenaviridae Lassa fever virus (hemorrhagic fever)
Deltavirus Hepatitis D (fulminant acute hepatitis)
ssRNA (+)
Picornaviridae Poliovirus (polio), rhinovirus (URI), Hepatitis A ("infectious" hepatitis)
Calciviridae Norwalk (gastroenteritis)
Hepevirus Hepatitis E (acute hepatitis)
Astroviridae Astrovirus (gastroenteritis)
Coronaviridae Coronavirus (respiratory infection)
Flaviviridae Yellow fever virus (yellow fever); Hepatitis C (hepatitis)
Togaviridae Eastern Equine encephalitis virus (encephalitis); Rubella virus (rubella)

Understanding Viruses

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