Definition and Properties of a Virus

•Viruses are filterable agents. •Viruses are obligate intracellular parasites. •Viruses cannot make energy or proteins independently of a host cell. •Viral genomes may be RNA or DNA but not both. •Viruses have a naked capsid or an envelope morphology. •Viral components are assembled and do not replicate by "division."

• Consequences of Viral Properties• Viruses are not living. • Viruses must be infectious to endure in nature. • Viruses must be able to use host cell processes

to produce their components (viral messenger RNA, protein, and identical copies of the genome).

• Viruses must encode any required processes not provided by the cell.

• Viral components must self-assemble.

• Means of Classification and Naming of Viruses• Structure: size, morphology, and nucleic acid (e.g.,

picornavirus [small RNA], togavirus) • Biochemical characteristics: structure and mode of

replication* • Disease: encephalitis and hepatitis viruses, for example • Means of transmission: arbovirus spread by insects, for

example • Host cell (host range): animal (human, mouse, bird),

plant, bacteria • Tissue or organ (tropism): adenovirus and enterovirus,

for example

           

                                                                                                                                                                                                         

                 

• Picornavirus • Togavirus• Retrovirus • Poxvirus• Adenovirus• Reoviruses• Norwalk virus• Coxsackie virus

           

                                                                                                                                                                                                         

                 

• The DNA viruses and their morphology. The viral families are determined by the structure of the genome and the morphology of the virion

           

                                                                                                                                                                                              

                            

The RNA viruses, their genome structure, and their morphology. The viral families are determined by the structure of the genome and the morphology of the virion. E, enveloped; N, naked capsid.

Viruses

• nm

• Parvovirus 18nm

• Poxvirus 300nm

           

                                                                                                                                                    

                                        

• Families of DNA Viruses and Some Important Members Family Members

• POXVIRIDAE Smallpox virus, vaccinia virus, monkeypox, molluscum contagiosum

• Herpesviridae Herpes simplex virus types 1 and 2, varicella-zoster virus, Epstein-Barr virus, CMV, human herpesviruses 6, 7, and 8

• Adenoviridae Adenovirus• Papilloma viridae Papilloma virus• Polyoma viridaeJC virus, BK virus,SV40• Hepadnaviridae Hepatitis B virus• Parvoviridae Parvovirus B19, adeno-associated virus

*The italicized virus is the important, or prototype, virus for the family.

           

                                                                                                             

                                        

           

                                                                                                                                              

                                        

Steps in Viral Replication• Recognition of the target cell • Attachment • Penetration • Uncoating • Macromolecular synthesis

– Early messenger RNA (mRNA) and nonstructural protein synthesis: genes for enzymes and nucleic acid-binding proteins

– Replication of genome – Late mRNA and structural protein synthesis – Post-translational modification of protein

• Assembly of virus • Budding of enveloped viruses • Release of virus

           

                                                                                                                                          

                                        

• Examples of Viral Attachment ProteinsVirus FamilyVirus VAP

• Picornaviridae Rhinovirus VP1-VP2-VP3 • Adenoviridae Adenovirus Fiberprotein • Reoviridae Reovirus σ1

Rotavirus VP7 • Togaviridae Semliki Forest vE1-E2-E3 complex

Rhabdoviridae Rabies virus G protein • Orthomyxoviridae Influenza A HA • Paramyxoviridae Measles virus HA • Herpesviridae Epstein-Barr v gp350 and gp220• Retroviridae Murine leukemia vgp7

Human immunodeficiency virusgp120

• gp, glycoprotein; HA, hemagglutinin; VAP, viral attachment protein.

• Examples of Viral Receptors • Virus Target Cell Receptor* • Epstein-Barr virus B cell C3d complement receptor CR2 (CD21) • HIV Helper T cell CD4 molecule and chemokine

coreceptor Rhinovirus Epithelial cells ICAM-1 (immunoglobulin superfamily protein)

• Poliovirus Epithelial cells Immunoglobulin superfamily protein • Herpes simplex virus Many cells Herpesvirus entry mediator (HVEA),nectin-1 • Rabies virus Neuron Acetylcholine receptor, NCAM (neural

cell adhesion molecule) • Influenza A virus Epithelial cells Sialic acid • B19 parvovirus Erythroid precursors Erythrocyte P antigen (globoside)

• *Other receptors for these viruses may also exist.ICAM-1, Intercellular adhesion molecule.

Mechanisms of Viral Pathogenesis Determinants of Viral Disease• Nature of the Disease • Target tissue • Portal of entry of virus • Access of virus to target tissue • Tissue tropism of virus • Permissiveness of cells for viral replication • Viral pathogen (strain) • Severity of Disease • Cytopathic ability of virus • Immune status • Competence of the immune system • Prior immunity to the virus • Immunopathology • Virus inoculum size • Length of time before resolution of infection • General health of the person • Nutrition • Other diseases influencing immune status • Genetic makeup of the person • Age

           

                                                           

                                                          

The stages of viral infection. The virus is released from one person, is acquired by another, replicates, and initiates a primary infection at the site of acquisition. Depending on the virus, it may then spread to other body sites and finally to a target tissue characteristic of the disease. B, The cycle starts with acquisition, as indicated, and proceeds until the release of new virus. The thickness of the arrow denotes the degree to which the original virus inoculum is amplified on replication. The boxes indicate a site or cause of symptoms. C, Time course of viral infection. The time course of symptoms and the immune response correlate with the stage of viral infection and depend on whether the virus causes symptoms at the primary site or only after dissemination to another (secondary) site. CMV, cytomegalovirus; HBV, hepatitis B virus; HIV, human immunodeficiency virus.

• Failed infection (abortive infection).

• Cell death (lytic infection).

• Replication without cell death (persistent infection).

Mechanisms of Viral Pathogenesis

• Determinants of Viral Pathogenesis• Interaction of Virus with Target Tissue • Access of virus to target tissue • Stability of virus in the body

– Temperature – Acid and bile of the gastrointestinal tract

• Ability to cross skin or mucous epithelial cells (e.g., cross the gastrointestinal tract into the bloodstream) • Ability to establish viremia • Ability to spread through the reticuloendothelial system • Target tissue

– Specificity of viral attachment proteins – Tissue-specific expression of receptors

• Cytopathologic Activity of the Virus • Efficiency of viral replication in the cell

– Optimum temperature for replication – Permissiveness of cell for replication

• Cytotoxic viral proteins • Inhibition of cell's macromolecular synthesis • Accumulation of viral proteins and structures (inclusion bodies) • Altered cell metabolism (e.g., cell immortalization) • Host Protective Responses • Antigen-nonspecific antiviral responses

– Interferon – Natural killer cells and macrophages

• Antigen-specific immune responses – T-cell responses – Antibody responses

• Viral mechanisms of escape of immune responses • Immunopathology • Interferon: flulike systemic symptoms • T-cell responses: delayed-type hypersensitivity • Antibody: complement, antibody-dependent cellular cytotoxicity, immune complexes • Other inflammatory responses