INTRODUCTION TO VIROLOGY

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INTRODUCTION TO VIROLOGY

• ANGELA AMEDEE, PH.D.
• November 16, 2005

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• WHAT IS A VIRUS?

From Latin for a slimy liquid, a poisonous
liquid
filterable agents Obligate intracellular
parasites RNA or DNA genome

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25 nm
300 nm
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VIRAL CLASSIFICATION

• Disease
• Mode of transmission
• Structure
• Biochemical characteristics
• The most consistent classification is by
  physical and biochemical characteristics such as
  type of genome (RNA or DNA), presence or absence
  of envelope. 

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• Virion the complete virus particle
• Capsid the protein coat surrounding the nucleic
  acid genome
• Capsomers the repeating protein subunits that
  make up the capsid
• Protomers the polypeptide chains which make up
  the capsomers

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4.MatureCapsid
1.Protomers
2.Capsomers
3.Pro-Capsid
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• Symmetry The viral capsid is assembled from
  individual proteins.  The arrangement of the
  capsid around its viral genetic material is
  unique for each type of virus.  The general
  properties of this arrangement define the shape
  and symmetry. 
• The simplest structures that can be built are
  helical and icosahedral.

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4.MatureCapsid
1.Protomers
2.Capsomers
3.Pro-Capsid
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Icosahedral Capsids
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Helical Capsids
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Viral Envelope

• Membrane composed of lipids, proteins,
  glycoproteins.
• Obtained from cellular membranes

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Icosahedral HelicalCapsid
Capsid
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Adenovirus Icosahedral Capsids
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HerpesEnvelopedIcosahedral Virus
HHV-1 Capsid approx. 100nm
Thin section of HHV-1 leaving the nucleus
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InfluenzaEnveloped Helical Virus
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HIVEnveloped Icosahedral
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VIRAL ATTACHMENT ENTRY
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External Viral Proteins attach to cell
receptors.Receptor proteins are usually normal
cellular surface components
ATTACHMENT
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Binding of Adenovirus
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ATTACHMENT OF HIV
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VIRAL ENTRY

• Fusion with cell membrane - at cell
  membrane - in an endosome
• Receptor-mediated endocytosis

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ENVELOPE PROTEINS OF INFLUENZA
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Target Cell
Cell Membrane
Endocytosis
Influenza virus
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GENERAL MODEL OF REPLICATION
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Picornavirus () RNA virus Genome used as mRNA
Rhabdovirus (-) RNA virus
Viral Polymerase produces mRNA
AAA
Viral polyprotein
Viral proteins
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REPLICATION OF PICORNAVIRUSES
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RABIES VIRUS REPLICATION
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VIRAL ENVELOPE
ASSEMBLY
BUDDING
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Budding of anEnveloped RNA Virus
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LIFE CYCLE OF HERPESVIRUS
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LIFE CYCLE OF HERPESVIRUS -continued
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VIRAL DISEASESTRANSMISSION EPIDEMIOLOGY
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MODES OF VIRUS TRANSMISSION

• Respiratory
• Fecal-Oral
• Contact (fomites, lesions, saliva)
• Zoonoses (insects and animals)
• Blood
• Sexual
• Materal-Neonatal

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Respiratory Transmission
Paramyxoviruses, Influenza, Rhinoviruses,Enterovi
ruses, Varicella-Zoster virus, B19 virus
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The Common Cold
Rhinoviruses, Coronaviruses, Adenoviruses
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INFLUENZA
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MEASLES (Paramyxovirus)

• 61 cases in US in 2005 (through Oct.)
• Worldwide, gt 30 million cases each year.
• gt 500,000 deaths in 2003.

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Current vaccine initiatives have dropped measles
rates by gt 60 in Africa
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Disease Course of Measles
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Varicella Zoster Virus (HHV-3)
Chicken Pox
Shingles
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Varicella Zoster VirusMechanism of Spread
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ACUTE common cold measles LATENT (Recurrent) var
icella zoster
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Fecal-Oral Transmission
Human Fecal Matter
Sewage
Hand
Solid wastelandfills
Water Supply
Shellfish
Picornavirus, Rotavirus, Reovirus, Caliciviruses,
Adenovirus
NEW HOST
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Transmission through Contact or Fomites
Rhinoviruses, Adenoviruses, Poxviruses
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Transmission through Blood or Injection
HIV, Hepatitis B, C, D, HTLV-1
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SEXUAL TRANSMISSION
HIV, Hepatitis, Herpes, Human Papilloma Virus,
HTLV-1
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HerpesvirusHHV-1, herpes simplex ICold Sore
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Adults and children estimated to be living with
HIV/AIDS as of end 2004
Eastern Europe Central Asia 1.4 million
Western Europe 610,000
North America 1 million
East Asia Pacific 1.1 million
South South-East Asia 7.1 million
North Africa Middle East 540,000
Caribbean 440 000
Sub-Saharan Africa 25.4 million
Latin America 1.7 million
Australia New Zealand35,000
Total 39.4 million
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CHRONIC Hepatitis B Chronic with Late
Disease HIV, HTLV-I SLOW
Shedding
Shedding
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Mother-Infant Transmission
HIV, Rubella, Herpes simplex, Cytomegalovirus,B19
, Varicella, Echovirus
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ZOONOSES
ARBOVIRUSESTogaviruses(alpha), Flaviviruses,
Bunyaviruses
Pox viruses
RABIES
Hantavirus
Orf
Deer Mouse
Bats, Raccoons Dogs
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Arboviral Encephalitisin Louisiana

• Infectious Disease
• Epidemiology Section
• Office of Public Health
• LA Dept of Health Hospitals
• ...Your Taxes at Work

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LA Headlines
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Louisiana 78 33 0 111
6 Totals in US 1053 1,363 165 2,581
83 As of 11/1/05
Deaths
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2005 West Nile Virus Activity in theUnited
States
reported to CDC as of 11/1/05
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The official U.S. government Web site for
information on pandemic flu and avian
influenza.www.pandemicflu.gov
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• Beijing shuts live poultry markets Monday,
  November 7, 2005 Posted 758 p.m. EST (0058
  GMT)

BEIJING, China (AP) -- China ordered the closure
of all live poultry markets in Beijing and
conducted door-to-door searches for chickens and
ducks as it toughened its efforts to fight bird
flu, and the World Health Organization warned
that a global human flu pandemic is inevitable.
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SARS Devastates Asias Livelihood
B A N G K O K, Thailand, April 19, 2003 The
SARS virus has now hit nearly every country in
Asia, spreading fear, panic, and economic chaos
in its wake.
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SARS
Characterization of a Novel Coronavirus
Associated with Severe Acute Respiratory Syndrome
Paul A. Rota 1, M. Steven Oberste 1, Stephan S.
Monroe 1, W. Allan Nix 1, Ray Campagnoli 1,
Joseph P. Icenogle 1, Silvia Peñaranda 1, Bettina
Bankamp 1, Kaija Maher 1, Min-hsin Chen 1,
Suxiong Tong 1, Azaibi Tamin 1, Luis Lowe 1,
Michael Frace 1, Joseph L. DeRisi 2, Qi Chen 1,
David Wang 2, Dean D. Erdman 1, Teresa C. T.
Peret 1, Cara Burns 1, Thomas G. Ksiazek 1,
Pierre E. Rollin 1, Anthony Sanchez 1, Stephanie
Liffick 1, Brian Holloway 1, Josef Limor 1, Karen
McCaustland 1, Melissa Olsen-Rassmussen 1, Ron
Fouchier 3, Stephan Günther 4, Albert D. M. E.
Osterhaus 3, Christian Drosten 4, Mark A.
Pallansch 1, Larry J. Anderson 1, William J.
Bellini 1 In March 2003, a novel coronavirus
(SARS-CoV) was discovered in association with
cases of severe acute respiratory syndrome
(SARS).
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EBOLA WHO announces end of Ebola outbreak in
southern Sudan 7 August 2004
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Bringing the Marburg Outbreak Under Control in
Angola
July 2005
Dr Mark Katz from the Centers for Disease Control
and Prevention, USA, takes a sample from a woman
for diagnostic testing.
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Monkeypox
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SmallpoxPoxvirus
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CONTROLLING VIRUS

• Prophylaxis is our best tool(preventive
  treatment).
• Vaccines
• Universal precautions for handlingof blood and
  body fluids. 
• Education

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Viral Vaccines
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Types of Viral Vaccines

• Live attenuated virus vaccines  - selected or
  genetically altered organisms that are avirulent
  (MMR -mumps, measles and rubella  combination,
  varicella-zoster, yellow fever,
• Killed or inactivated vaccines  -inactivation
  with formalin or disrupted with detergents  
  (polio Salk influenza A and B, hepatitis A,
  and rabies).
• Recombinant/subunit vaccine. -non-living
  vaccines-vira genes expressed in yeast. 
  -assembles into typical virus-like particles.

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Vaccines Currently not in use in theUnited
States
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New Vaccine Approaches

• DNA vaccines
• Hybrid virus vaccines/viral vectors
• Virus-like particles (VLPs)
• Anti-idiotype antibodies
• Production of viral proteins in eukaryotic cells
• Peptide subunit vaccines

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Mechanisms of Viral Pathogenesis
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• ?Lytic infections are viral infections that kill
  the cell. Cell death may be by many different
  mechanisms, such as apoptosis.
• ?Persistent infections do not cause cell death
  and may be chronic, latent, recurrent or
  transforming.  For a virus to establish a
  persistent infection, it must be able to limit
  its cytolytic effects, maintain its genome within
  host cells, and avoid elimination by the hosts
  immune system.

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Mechanisms of Viral Cytopathogenesis
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• Syncytia a mass of cytoplasm containing several
  nuclei.  The expression of cell surface
  glycoproteins of some viruses like HIV,
  herpesviruses and Respiratory Syncytial Virus (a
  paramyxoviruse) can trigger the fusion of
  neighboring cells into multinucleated giant cells
  called syncytia.

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Syncytia caused by Respiratory Syncytial Virus
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Negri bodies Rabies Virus
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VIRAL QUASISPECIES

• VIRAL QUASISPECIES is a heterogeneous group of
  sequences clustering around a consensus.
• Important for virus emergence, drug resistance
  and vaccine escape.

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Laboratory Diagnosis of Viral Disease
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Laboratory Diagnosis of Viral Disease

• Observation of cytopathic effects
• Electron microscopic detection
• Isolation and growth of the virus
• Detection of viral components (nucleic acid,
  protein, enzymes)
• Serology

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Culture of Virus
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Cytopathic Effects of HSV
Uninfected
Infected
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Cell Culture Inoculation
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Following growth of the virus, cells are removed
and stained with Flourescent Antibodies
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CMV Infected Cells
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Observation by Electron Microscope
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Screening of Donated Blood Detection of HIV and
Hepatitis Antibodies by EIA
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ELISA
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Western Blot
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PCR (polymerase chain reaction)
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GENE CHIPS Diagnostics of the Future
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Viral Plaques
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