Size Size and and Shape Shape of of Viruses Viruses
• Methods • Size of Viruses • Shapes of Viruses
Methods of Analysis Electron microscopy : The resolution is 5nm (1nm = 10-9 m) X-ray crystallography
Size of Viruses Viruses are the smallest infectious agents and contain only one kind of nucleic acid (RNA or DNA) as their genome. A small virus has a diameter of about 20nm. Parvovirus A large virus have a diameter of up to 400nm. Poxviruses
A 、 Bacteriophage ( 65 ×95nm ) B 、 Adenovirus (70nm )
Rickettsia 450nm
Chlamydia 390nm A
S.aureus (1000nm )
C 、 Poliovirus (30nm )
G F
Cowpox 300×250nm
B
E
C D
D 、 JEV ( 40nm ) E 、 Protein (10nm )
F 、 Influenza virus ( 100nm )
G 、 TMV
Shape of Viruses • • • • • •
Spherical Rod-shaped Brick-shaped Tadpole-shaped Bullet-shaped Filament
Shapes of Viruses:Spherical
Shapes of Viruses :Rod-shaped
Shapes of Viruses :Brick-shaped .
Tadpole-shaped
Shapes of Viruses :Bullet-shaped
Shapes of Viruses :Filament
Structure of Viruses
Virion • the complete infectious unit of virus particle • Structurally mature, extracellular virus particles.
The simplest of virus particles consists of a protein coat (capsid) which surrounds a strand of nucleic acid and are thus called naked viruses or nucleocapsid.
More complicated viruses have their nucleic acid surrounded by a protein coat which is further engulfed in a membrane structure envelope and are thus called enveloped viruses
Virion envelope
Capsid
Viral core
Viral core • Viral core The viral nucleic acid genome, In the center of the virion. Control the viral heredity and variation, responsible for the infectivity.
Genome genome of a virus can be either DNA or RNA • DNA-double stranded (ds): linear or circular Single stranded (ss) : linear or circular • RNA- ss:segmented or non-segmented ss:polarity+(sense) or polarity –(non-sense) ds: linear (only reovirus family)
Viral Capsid • The nucleic acid is surrounded by a protein coat called a capsid, made up of subunits called capsomers. The arrangement of csapsomers gives the virus structure its geometric symmetry. There are three forms of symmetry in virus capsids: icosahedral , helical and complex forms. Helical structures appear as rods, whereas the icosahedron is an approximation of a sphere assembled from symmetrical subunits. 。 Nonsymmetrical capsids are complexforms and are associated with certain bacterial viruses (phages)
Viral Capsid Functions: a. Protect the viral nucleic acid. b. Participate in the viral infection. c. Share the antigenicity
Nucleocapsid (naked viruses) • The core of a virus particle consisting of the genome plus a complex of proteins. • complex of proteins = Structural
proteins +Non- Structural proteins (Enzymes &Nucleic acid binding proteins)
Symmetry of Nucleocapsid • Helical • Cubic /Icosahedral • Complex
Helical symmetry
Cubic or icosahedral symmetry
The icosahedron has 20 faces (each an equilateral triangle ) ,12 vertices
Complex Virus Structures • A well known example is the tailed bacteriophages such as T4. • The head of these viruses is cubic with a triangulation number of 7. This is attached by a collar to a contractile tail with helical symmetry.
Bacteriophage
Properties of naked viruses • • • • •
Stable in hostile environment Not damaged by drying, acid, detergent, and heat Released by lysis of host cells Can sustain in dry environment Can infect the GI tract and survive the acid and bile • Can spread easily via hands, dust, fomites, etc • Can stay dry and still retain infectivity • Neutralizing mucosal and systemic antibodies are needed to control the establishment of infection
Naked viruses( Non Enveloped ) • Adeno-associated Virus (AAV) Adenovirus B19 Coxsackievirus - A Coxsackievirus - B Echovirus Hepatitis A Virus (HAV) Hepatitis E Virus (HEV) Norwalk Virus
Envelope (enveloped viruses) • A lipid-containing membrane that surrounds some viral particles. • It is acquired during viral maturation by a budding process through a cellular membrane, Viruses-encoded glycoproteins are exposed on the surface of the envelope. • Not all viruses have the envelope, and viruses can be divided into 2 kinds: enveloped virus and naked virus.
Functions of envelope • Antigenicity some viruses possess neuraminidase • Infectivity • Resistance
Envelope
Properties of enveloped viruses • Labile in dry , arid environment • Damaged by drying, acid, detergent, and heat • Pick up new cell membrane during multiplication • Insert new virus-specific proteins after assembly • Virus is released by budding
Consequences of Properties for enveloped viruses • Must stay moist • Must not infect the GI tract for survival • Must be transmitted in the protective, droplets, secretions, blood and body fluids • Must reinfect another host cell to sustain • Humoral and cell-mediated immunity are needed to control the infection
Enveloped • • • • • •
• • •
• Herpes Simplex Virus 2 California Encephalitis Virus (HHV2) Coronavirus Human Immunodeficiency Cytomegalovirus (CMV) Virus (HIV) Eastern Equine Encephalitis Virus Human T-lymphotrophic Virus (EEEV) (HTLV) Epstein-Barr Virus (EBV) Influenza Virus (Flu Virus) Molluscum contagiosum Hantavirus Papilloma Virus (HPV) Hepatitis B Virus (HBV) Polio virus Hepatitis C Virus (HCV) Rhinovirus Hepatitis Delta Virus (HDV) Varicella-Zoster Virus (HHV3) Herpes Simplex Virus 1 (HHV1) Venezuelan Equine Encephal. Rotavirus Vir. (VEEV) Rubella Virus Western Equine Encephalitis Virus (WEEV) Saint Louis Encephalitis Virus Yellow Fever Virus Smallpox Virus (Variola) Vaccinia Virus
Spike or Peplomere: Furthermore, there are frequently glycoproteins in the form of spike like projections on the surface, which attach to host cell receptors during entry of the virus into the cell.
summarize
Virion structure • Nucleocapsid (Naked Virus) = DNA or RNA +Structural proteins +Enzymes &Nucleic acid binding proteins • Enveloped Virus =Nucleocapsid+ Viral specific glycoproteins and Host Membrane
Cubic
Helical
Naked Virus
Envelope d Virus
CHEMICAL COMPOSITION OF VIRUSES • • • •
Viral Protein Viral Nucleic Acid Viral Lipids Viral carbohydrate
Viral Protein • Structural protein (Capsomere) • Enzyme • glycoproteins (spike/viral attachment protein, VAP)
The structural proteins of viruses They include capsid proteins and enzymes as well as basic core proteins which may be necessary to package the nucleic acid within the capsid. The structural proteins ( capsid ) have several important functions. Their major purpose is to facilitate transfer of the viral nucleic acid from one host cell to another. They serve to protect the viral genome against inactivation by nucleases.
participate in the attachment of the virus particle to a susceptible cell, and provide the structural symmetry of the virus particle. The proteins determine the antigenic characteristics of the virus. The host's protective immune response is directed against antigenic determinants of proteins or glycoproteins exposed on the surface of the virus particle. Some surface proteins may also exhibit specific activities, e.g., influenza virus hemagglutinin agglutinates red blood cells.
Some viruses carry enzymes inside the virions. Examples include an RNA polymerase carried by viruses with negative-sense RNA genomes that is needed to copy the first mRNAs, and reverse transcriptase, an enzyme in retroviruses that makes a DNA copy of the viral RNA.
The non-structure proteins they are other protein such as enzymes that are needed for the production of viral components but are not part of the virion
Viral Nucleic Acid • DNA-double stranded (ds): linear or circular Single stranded (ss) : linear or circular • RNA- ss:segmented or non-segmented ss:polarity+(sense) or polarity –(non-sense) ds: linear (only reovirus family)
Viral Envelopes • A number of different viruses contain lipid envelopes as part of their structure. The lipid is acquired when the viral nucleocapsid buds through a cellular membrane in the course of maturation. Budding occurs only at sites where virusspecific proteins have been inserted into the host cell membrane.
The budding process varies markedly depending on the replication strategy of the virus and the structure of the nucleocapsid. The specific phospholipid composition of a virion envelope is determined by the specific type of cell membrane involved in the budding process. For example, herpesviruses bud through the nuclear membrane of the host cell, and the phospholipid composition of the purified virus reflects the lipids of the nuclear membrane.
Viral Glycoproteins • Viral envelopes contain glycoproteins. In contrast to the lipids in viral membranes, which are derived from the host cell, the envelope glycoproteins are virus-encoded. However, the sugars added to viral glycoproteins often reflect the host cell in which the virus is grown
Replication Replication of of Viruses Viruses
The viral nucleic acid contains information necessary for programming the infected host cell to synthesize virus-specific macromolecules required for the production of viral progeny.
As obligate intracellular parasites, Virus must enter and replicate in living cells in order to “reproduce” themselves. This “growth cycle” involves specific attachment of virus, penetration and uncoating, nucleic acid transcription, protein synthesis, maturation and assembly of the virions and their subsequent release from the cell by budding or lysis
Initiation Phase • Attachment • Penetration • Uncoating
Attachment/Adsorption • Virus attaches to the cell surface. Attachment is via ionic interactions which are temperatureindependent. • Viral attachment protein recognizes specific receptors on the cell surface (These may be protein or carbohydrate or lipid components of the cell surface). • Cells without the appropriate receptors are not susceptible to the virus.
PENETRATION (Virus enters the cell) • Virions are either engulfed into vacuoles by “endocytosis” or the virus envelope fuses with the plasma membrane to facilitate entry • Enveloped viruses • Non-enveloped viruses
Fusing • (A) Entry by fusing with the plasma membrane. Some enveloped viruses fuse directly with the plasma membrane. Thus, the internal components of the virion are immediately delivered to the cytoplasm of the cell.
HIV
Endocytosis • (B) Entry via endosomes at the cell surface
influenza virus
Enveloped viruses •
Some enveloped viruses require an acid pH for fusion to occur and are unable to fuse directly with the plasma membrane. These viruses are taken up by invagination of clathrin coated pits into endosomes. As the endosomes become acidified, the latent fusion activity of the virus proteins becomes activated by the fall in pH and the virion membrane fuses with the endosome membrane. This results in delivery of the internal components of the virus to the cytoplasm of the cell
Non-enveloped viruses • Non-enveloped viruses may cross the plasma membrane directly • may be taken up via clathrin-coated pits into endosomes. They then cross (or destroy) the endosomal membrane.
unenveloped viruses
UNCOATING • Nucleic acid has to be sufficiently uncoated that virus replication can begin at this stage. When the nucleic acid is uncoated, infectious virus particles cannot be recovered from the cell - this is the start of the ECLIPSE phase - which lasts until new infectious virions are made • Uncoating is usually achieved by cellular proteases “opening up” the capsid
BIOSYNTHESIS • genome synthesis • mRNA production • protein synthesis
Maturation assembly release
Maturation • The stage of viral replication at which a virus particle becomes infectious; nucleic acids and capsids are assembled together.
ASSEMBLY • The stage of replication during which all the structural components come together at one site in the cell and the basic structure of the virus particle is formed.
RELEASE •
Disintegration : naked virus cause the host cell lysis • Budding: enveloped viruses
• Budding viruses do not necessarily kill the cell. Thus, some budding viruses may be able to set up persistence
Assembly
Products of viral replication • Virion • DEFECTIVE VIRUS • ABORTIVE INFECTION • integration
• DEFECTIVE VIRUS A defective virus is one that lacks one or more functional genes required for viral replication. Defective viruses require helper activity from another virus for some step in replication or maturation.
ABORTIVE INFECTION Not all infections lead to new progeny virus. Productive infections occur in permissive cells and result in the production of infectious virus. Abortive infections fail to produce infectious progeny, either because the cell may be nonpermissive and unable to support the expression of all viral genes or because the infecting virus may be defective, lacking some functional viral gene. A latent infection may ensue, with the persistence of viral genomes, the expression of no or a few viral genes, and the survival of the infected cell.
Classification Classification of of Viruses Viruses
CLASSIFICATION OF VIRUSES -------basis of classification • • • • • • •
Virion morphology Physicochemical properties of the virion Virus genome properties Virus protein proteries Genome organization and replication Antigenic properties Biologic properties
CLASSIFICATION OF VIRUSES • By 1995 --71 families, 11 subfamilies --164 genera • For humans and animals --24 families, --DNA: 7; RNA: 17 for humans
Survey of DNA-containing Viruses • • • • • •
Parvoviruses: human parvovirus B Papovaviruses: papillomaviruses Adenoviruses: 47 types infect humans Herpesviruses: human herpesvirus 1-8 Poxviruses: smallpox; vaccinia Hepadnaviruses: HBV 19
Survey of RNA-containing Viruses • • • • • • • • •
Picornaviruses Astroviruses Caliciviruses Reoviruses Arboviruses Togaviruses Flaviviruses Arenaviruses Coronaviruses: SARS
• • • • • • • • •
Retroviruses Bunyaviruses Othomyxoviruses Paramyxoviruses: Rhabdoviruses:rabies virus Bornaviruses: BDV Filoviruses Other viruses Viroids
Viroids • Viroids are small (200-400nt), circular RNA molecules with a rod-like secondary structure which possess no capsid or envelope which are associated with certain plant diseases. Their replication strategy like that of viruses - they are obligate intracellular parasites.
Prions • Prions are rather ill-defined infectious agents believed to consist of a single type of protein molecule with no nucleic acid component. Confusion arises from the fact that the prion protein & the gene which encodes it are also found in normal 'uninfected' cells. These agents are associated with diseases such as Creutzfeldt-Jakob disease in humans, scrapie in sheep & bovine spongiform encephalopathy (BSE) in cattle.