BRIEF HISTORICAL BACKGROUND 1 History 1 The existence

BRIEF HISTORICAL BACKGROUND 1

History 1 �The existence of viruses became evident during the closing years of the 19 th century, as a result of a newly acquired expertise in the handling of bacteria, �The infectious agents of numerous diseases, were being isolated. �For some infectious diseases, this proved to be an elusive task until it was realized that the agents causing them were 2

History 2 �Iwanowski 3 (1892), was probably the first to record the transmission of an infection, “tobacco mosaic disease” by a suspension filtered through a bacteria-proof filter. �This was followed in 1898 by similar experiment of Loffler and Frosch concerning foot and mouth disease of cattle

History 3 �Beijerinck (1898) considered the infectious agents in bacteria-free filtrates to be living but fluid, that is nonparticulate, and introduced the term “virus” (meaning poison in Latin) to describe them. �It 4 quickly became clear, however, that viruses were particulate and the term “virus” became the operational definition of infectious agents smaller than bacteria and unable to multiply outside living cells

History 4 �In 1911, Rous discovered a virus that produced malignant tumors in chickens, �During World War I (1915, 1917) Twort and d’Herrelle independently discovered the viruses that multiply in bacteria, the bacteriophages. 5

Experimental approaches � During 6 the next 25 years, the experimental approaches in the different areas of virology diverged � Plant viruses proved easy to obtain in large amounts, thus permitting extensive chemical and physical studies. � This work first led to the demonstration that plant viruses consist only of nucleic acid and protein and culminated in the crystallization of tobacco mosaic virus (TMV) by Stanely in 1935. � This feat evoked a great surprise since it cut across preconceived ideas concerning the attributes of living organisms and demonstrated that agents able to reproduce in living cells behaved under certain

Experimental approaches �Work with bacteriophages concentrated on their clinical applications. �It was hoped that bacteria could be destroyed inside the body by injecting appropriate bacteriophages. �Their activity, however, never matched their activity in vitro, most probably because they are eliminated efficiently from the bloodstream. 7

Breakthroughs �Around the year 1940 came several ◦breakthroughs: First, the introduction of electronmicroscopy permitted visualization of viruses for the first time. �As will become evident, not only morphology an important criterion of virus classification, but the study of the morphology of viruses has also profound impact on our understanding of their behavior and function. 8 ◦ Second, techniques for purifying certain animal viruses were being perfected.

Breakthroughs ◦ Third, Hirst(1941) discovered that influenza virus agglutinates chicken red blood cells. �This phenomenon, “hemagglutination” was rapidly developed into an accurate method for quantitating myxoviruses, as a result of which this group of viruses became in the 1940 s the most intensively investigated group of animal viruses. 9 ◦ Finally, this period marked the beginning of the modern era of bacterial virology.

Virology and Advances in Molecular Biology �Indeed, during the last four decades of the previous century, many of the major advances in molecular biology have resulted from work in the bacteriophage field. Among these are: 10 ◦ The demonstration that initiation of virus infection involves the separation of viral nucleic acid and protein, ◦ The demonstration that the virus genome can become integrated into the genome of the host cell, ◦ The discovery of messenger RNA, and the elucidation of factors that control initiation and termination of both

�In animal virology, rapid advances followed the development in the 1940 s, of techniques for growing animal cells in vitro. �Strains of many types of mammalian cells can now be grown in media of defined composition. �As a result, animal cell-virus interactions can now be analyzed with the same techniques that have proved so powerful in the case of bacteriophages. �Many new techniques have been used for purification and identification of viruses ◦ e. g density gradient ultracentrifugation, 11

GENERAL PROPERTIES AND CLASSIFICATION OF VIRUSES 12

What are Viruses? �They 13 are small, nanometer “nm” is the measuring unit. �Obligate intracellular parasites. �They possess only one species of nucleic acid, either DNA or RNA. �They have receptor-binding protein for attaching to host cells. �Viruses colonize most living beings, whether plant,

Viruses � They are small, nanometer “nm” is the measuring unit (20 -300 nm)

Basic Components of Viruses �Viral particles consist of two or three parts: 1. Genome, “nucleic acid, DNA or RNA” 2. Protein coat called capsid which is made up of capsomeres. �Capsid protects the genome. ◦ The nucleic acid core and the capsid are together known as nucleocapsid. ◦ The complete virus particle is termed virion. 3. Envelope, composed of lipids and proteins. �Envelope is derived from plasma membrane of the host cell. �Spikes, may be present on the outer surface of the virus. �They mediate attachment to host cell receptors. 15

Basic Components of Viruses 16

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

Viruses Show Two Main Forms of Symmetry �Icosahedral ◦ symmetry- capsomeres are arranged to form a solid with 20 equal triangular sides �Helical symmetry◦ capsomeres are arranged like the steps in a spiral staircase around the central genome core 18

Complex Viruses �Viruses with large genomes have complex architecture. �Poxviruses have lipids in both the envelopes and the outer membranes of the viruses; 19 ◦ they are neither icosahedral nor helical, and are referred to as complex viruses.

Five Basic Structural Forms of Viruses in Nature • Naked icosahedral • e. g. poliovirus, adenovirus, hepatitis A virus • Naked helical • e. g. tobacco mosaic virus. So far no human viruses with this structure are known • Enveloped icosahedral • e. g. herpes virus, yellow fever virus, rubella virus • Enveloped helical • e. g. rabies virus, influenza virus, parainfluenza virus, mumps virus, measles virus • Complex • e. g. Bacteriophage, poxvirus

Virus Genome �Nucleic acid molecules may be: ◦ DNA or RNA �Double-stranded or single stranded �Linear, circular, continuous or segmented ◦ Most DNA viruses are double-stranded ◦ Most RNA viruses are single-stranded �Single-stranded RNA viruses are either: 22 �positive stranded (“+” sense RNA); can act directly as m. RNA, �or negative-stranded (“-“ sense RNA); must be transcribed by a virus-associated RNA transcriptase enzyme to a mirror-image (complementary) positivestranded copy, which is then used as m. RNA.

Virus Genome �The size of viral genome varies; ◦ the largest, e. g. , poxviruses may contain several hundred genes ◦ whereas, the smallest may have the equivalent of only 3 or 4 genes. 23

Classes of viruses �There are three major classes of viruses: ◦ Animal viruses, ◦ Plant viruses, and ◦ Bacterial viruses 24

Classification of Viruses �Criteria used for classification ◦ Nucleic acid type (DNA or RNA) ◦ The number of strands of nucleic acid and their physical construction �(single-or double-stranded, linear or circular, circular with breaks, segmented). ◦ Polarity of the viral genome; (+)-sense RNA or (-) -sense RNA. ◦ The symmetry of the nucleocapsid. ◦ The presence or absence of a lipid envelope. 25

Classification of Viruses 26

Classification of Viruses �According to the above-mentioned criteria, viruses are grouped into families (Tables 1 & 2), subfamilies, and genera. �Figures 4 represents types & forms of RNA & DNA virus genomes. �Further subdivision is based on the degree of antigenic similarity. 27

segmented Figure 4: Types & forms of RNA & DNA virus genomes 28

Nomenclature of Viruses �Some viruses are named according to the type of disease they cause, ◦ e. g. , poxviruses and herpesviruses �Other family names are based on acronyms, ◦ e. g. , papovaviruses “papillomapolyoma-vacuolating agent” and picornaviruses “pico=small; rna= ribonucleic acid”. �Others 29 are based on morphological features of the virion,

Nomenclature of Viruses �Some viruses are named after the place where they were first isolated, ◦ e. g. , Coxsackie and Marburg viruses. �Some viruses are named after their discoverers, ◦ e. g. , Epstein-Barr virus. 30

Nomenclature of Viruses �The official nomenclature of families and sub-families is Latinized ◦ e. g. , Picornaviridae, Poxviridae. �A few families are divided into subfamilies with the suffix – virinae, ◦ e. g. , chordopoxvirinae. �Genera are not latinized, and they have the suffix virus, ◦ e. g. , orthopoxvirus, parapoxvirus 31