module 10a virology

Virology

Morphology & Background

Common viruses

Viral Diseases

Choose me !!!!!!

Background Information:)

■ virus are parasites, not cells

■ virus are packages of genetic info - nucleic acids in protein coats

■ virus only supplies information, rest is dependent on host

■ all cells can be parasitized by virus, they only attack closely related organisms

■ virus comes from a latin word “poison” or “slime”

What are viruses?

■ virus = “poison”■ with genetic material (DNA or RNA) and

protein coat (capsid).■ obligatory intracellular parasites.■ infect the cells of a biological organisms.■ they replicate by using the host cell’s

metabolic“machinery”.

Definition of Terms:

■ Capsid- protein shell, or coat, that encloses the nucleic acid genome

■ Capsomere – Morphologic units of virus seen under the EM on the surface of icosahedral virus particles• Represents clusters of polypeptide

■ Defective virus – virus particle that is functionally deficient in some aspect of replication

More terms:

■ Envelope – lipid containing membrane that surrounds some virus particles• Acquired during viral maturation by a

budding process thru a cellular membrane

■ Nucleocapsid – protein nucleic acid complex representing the packaged form of the viral genome

■ Subunit – single folded viral polypeptide chain

■ Structural units – Basic protein building blocks of the coat. • Usually a collection of more than one

nonidentical protein unit.

• The structural unit is often referred to a protomer.

■ Virion – Complete virus particle. In some instances, the virion is identical to the nucleocapsid. In more complex virions, this includes the nucleocapsid plus a surrounding envelope.

Background Information:

■ Dmitri Iwanowski - 1892 first isolation of TMV

■ Martinus Beijerinck - filterable viruses

■ Wendell Stanley - 1935 purified & crystallized TMV

■ Are viruses alive?? they contain macromolecules but does not reproduce directly --- virions are intact, non-replicating virus particles ( no life)

Basis of classification

■ Virus morphology• Size• Shape• Type of symmetry

• Presence & absence of peplomers

• Presence & absence of membranes

■ Virus genome properties• Nucleic Acid ( DNA

or RNA )• Size of genomes in

kb (kilobase pairs )• Strandedness (single

or double )

• Nucleotide sequence

Basis for Classification:

■ Host Range• Plant virus

• Animal Virus• Bacteriophage

• Specificity cultivars ( plants), race or strains, receptors (protein)

■ Size • 25 nm to 300 nm• 1/10 to 1/3 of

bacteria• no cytoplasmic

structures• can be 77 genes

or 3 genes but still very lethal

SIZE■ Most viruses with capsid = between 10-300 nm

Structure:

■ Nucleic Acid core surrounded by protein

■ Viral Envelope - naked or enveloped

■ Nucleic Acid - DNA or RNA

■ Genome organization & replication• Gene order• Gene number

• Position of open reading frames

• Patterns of replication

• Cellular sites

■ Antigenic properties■ Biologic properties

including :• Natural host range• Mode of

transmission• Vector relationship• Pathogenecity• Tissue tropisms

• Pathology

■ Physiochemical Properties of the virion• Molecular mass• Buoyant density

• pH stability• Thermal stability• Susceptibility to agents

– Ethers– Detergents

■ Virus protein properties• Number• Size• Functional activities

• Amino acid sequence

• Modifications & special functions

– Transcriptase– Reverse trans.– Neuramidase– fusion

Types of Structure

■ Four morphological types:• 1. Helical Viruses

• 2. Icosahedral viruses • 3. Enveloped viruses • 4. Complex viruses

Helical virus

-Resemble long rods, may be rigid or flexible

-Viral nucleic acid found within a hollow cylindrical capsid.

-with single type of protomers stacked around a central axis to form a tube; eg. Tobacco mosaic virus.

Icosahedralspherical appearance but capsomeres arranged in a geometrical pattern like a soccer ball; eg.hepatitis B

Enveloped

with outer lipid layer = viral envelope

Complex

-- with extra structure such as protein tails, complex outer walls; eg. Bacteriophages, Poxviruses.

Life Cycle:■ outside the host there is no replication■ Stages :

• -->Adsorption

• --> Penetration • --> Uncoating• --> Viral synthesis

• --> Maturation • --> Release

Multiplication of Viruses

■ Lytic cycle – ends with the lysis and death of the host cell.

■ Lysogenic cycle- host cell remains alive

Taxonomy:

■ ICTV - International Committee on Taxonomy of Virus

■ Family Name -- Viridae -- Retroviridae■ Genus -- Virus -- Lentivirus■ Specie -- English -- HIV

■ Hepadnaviridae -- 7 DNA - Hepatitis

Misc. Information:

■ Replication applicable to all virus■ Plaque count - PFU Plaque forming

units■ One Step Growth Phase -- Latent --->

Burst Period

Common viruses in animals:

■ Line 1 - Family ■ Line 2 - Classification based on N.A.■ Line 3 - Properties■ Line 4 - Virus (species or Genus)■ Line 5 - Diseases

*** Legend

■ Herpesviridae■ DNA virus■ Enveloped dsDNA■ Herpes simplex 1&2,

Varicella zoster, EBV, cytomegalovirus CMV

■ cold sores, genital herpes, shingles, mononucleosis, birth defects

■ Poxviridae■ DNA virus■ Enveloped dsDNA■ Smallpox virus■ Smallpox ( variola )

■ Hepadnaviridae■ DNA virus■ Enveloped dsDNA■ Hepatitis B virus■ Hepatitis B

New Nomenclature for Hepatitis Virus■ Hepatitis A

• HAV virus• Etiologic agent of infectious Hepatitis

• A picornavirus, the prototype of a new genus, Hepatovirus

• Anti-HAV – antibody to HAV. Detectable at onset of symptoms; lifetime persistence

• IgM antibody

Hepatitis B

■ HBV- Hepatitis B virus

■ Etiologic agent of serum hepatitis

■ A hepadnavirus■ HBsAg, HBeAg,

HBcAg

■ Antibodies for Hep B• Anti-HBs• Anti-HBe• Anti-HBc

• IgM class Antibody

Hepatitis C

■ HCV – Hepatitis C Virus■ A common etiologic agent of post

transfusion hepatitis■ A Flavivirus, genus Hepacivirus■ Anti-HCV – antibody to HCV

Hepatitis D

■ Hepatitis D Virus■ Etiologic agent of delta hepatitis■ Causes infection only in presence of

HBV■ HDAg – Delta antigen, detectable only

in early acute HDV infection■ Anti-HDV - Antibody

Hepatitis E

■ HEV – Hepatitis E Virus■ Enterically transmitted hepatitis virus■ Causes large epidemics in Asia, North

& West Africa and Mexico■ Fecal-oral or waterborne infection■ Unclassified

■ Papoviridae■ DNA virus■ naked dsDNA■ Human papillomaviruses■ Warts

Polyomaviruses

■ Small (45nm ) naked, heat stable, ether resistant virus

■ Cubic symmetry with 72 capsomeres■ Circular, double stranded DNA■ JC virus, BK virus, SV40 virus■ Formerly part of Papoviridae family

■ Adenoviridae■ DNA virus■ Naked dsDNA ■ Human adenovirus■ respiratory, enteric

diseases, infectious pinkeye

Parvovirus

■ Naked Single stranded DNA virus■ Cubic symmetry with 32 capsomeres■ 5.6 kb in size■ Requires the presence of adenovirus or

herpesvirus as helper ( defective )

■ Retroviridae■ RNA virus■ Enveloped + strand RNA■ HIV-1 & 2, HTLV-1 &2■ AIDS , T cell leukemia

Life Cycle of HIV Virus

Astroviruses

■ 28-30 nm in diameter■ Exhibit a distinctive star-like morphology

under the EM■ Ss + sense RNA, 6.4 – 7.4 kb in size■ Causes diarrheal illnesses■ Transmitted by fecal-oral route thru

contaminated food or water

Arboviruses (arthropod borne)

■ Arenaviridae■ Bunyaviridae■ Flaviviridae■ Filoviridae■ Reoviridae■ Togaviridae

Arenaviruses

■ Generally associated with rodent-transmitted disease in humans.

■ Each virus usually is associated with a particular rodent host species in which it is maintained

■ Divided into two groups: • the New World or Tacaribe complex • the Old World or LCM/Lassa complex.

Filoviruses

■ Flaviviridae■ RNA virus■ enveloped +

strand RNA■ Yellow & Dengue

fever , Hep C virus

■ Yellow & Dengue fever, Hepatitis C

Prevention of Dengue

Types of Dengue

■ Non-fatal dengue fever (DF)■ Fatal Dengue Hemorrhagic fever (DHF)■ Dengue Shock Syndrome ( DSS)

Serotypes of Dengue

■ 4 serotypes■ DEN-1, DEN-2, DEN-3, DEN-4■ DEN-2 shows greatest antigenic and

genotypic distance from the others■ Protective immunity after infection is

homotypic

(Which means if your really unlucky u can have dengue __ times.)

More types of Flavivirus

■ Eastern & Western Encephalitis■ St. Louis Encephalitis■ West Nile Fever■ Japanese B Encephalitis■ Yellow Fever

■ Reoviridae■ RNA virus■ naked dsRNA■ Rotavirus■ Infant diarrhea

■ Bunyaviridae■ RNA virus■ Enveloped - strand

RNA■ Hantavirus■ Respiratory

distress syndrome

■ Togaviridae■ RNA virus■ Enveloped +

strand RNA■ Alphavirus, Rubella

virus■ encephalitis,

Rubella (German measles)

Picornaviruses

■ Enterovirus• Transient inhabitants

of the human alimentary tract

• Poliovirus• Coxsackie virus

• Paraechovirus– Echovirus 22– Echovirus 23

■ Rhinovirus• Isolated chiefly from

the throat and nose• More than 100

species based on receptors

– ICAM -1– LDLR

■ Picornaviridae■ RNA virus■ Naked + strand RNA■ Enterovirus, Poliovirus,

echovirus, Rhinovirus, hepatitis A virus

■ Polio, Myocarditis, pericarditis, colds, Hepatitis A

■ Coronaviridae■ RNA virus■ Enveloped +

strand RNA ■ Coronavirus■ upper respiratory

tract infections

■ Calciviridae■ RNA virus■ naked + strand

RNA■ Norwalk Agents■ Gastroenteritis

■ Orthomyxoviridae■ RNA virus■ Enveloped - strand RNA■ Influenza virus■ Influenza

■ Rhabdoviridae■ RNA virus■ enveloped - strand

RNA■ Rabies virus■ Rabies

■ Paramyxoviridae■ RNA virus■ enveloped - strand

RNA■ Mumps, measles virus,

Parainfluenza virus, Respiratory syncitial vir.

■ mumps, rubeola, Croup, Bronchiolitis

Recent Viral Diseases

■ SARS- severe acute respiratory syndrome

Avian Flu- spread of H5N1 strain

Influenza Pandemic (1918-1919)

– TEM of Spanish Influenza Virus (negatively-stained); subtype H1N1; H2N2; H3N2

25 million deaths in 25 weeks

20% of world population affected.

1957-1958

1968-1969

Next pandemic ????

Virus entry into an animal cell

What other roles could be attributed to viruses other than being pathogens?

■ Basic research, molecular biology and biotechnology

■ Horticulture■ Cross- protection■ Gene therapy■ Phage therapy■ Viro-therapy

Continuation……..

■ Material Science and Nanotechnology- In April 2006, MIT scientists created nanoscale metallic wires using a genetically-modified virus. The MIT team was able to use the virus to create a working battery with an energy density up to three times more than current materials. The potential exists for this technology to be used in liquid crystals, solar cells, fuel cells, and other electronics in the future.

■ Biological warfare- synthesis/recreation of viruses in laboratory (eg. 1918 flu virus, smallpox virus- Variola major)