1. Basic virology Chapter 28 Structure Prepared by : Ibtihal El-agha

2.  The viral nucleic acid (genome) is located internally.  It can be either single- or double-stranded DNA or single- or double-stranded RNA.  The nucleic acid can be either linear or circular. VIRAL NUCLEIC ACIDS :

3.  The DNA is always a single molecule.  The RNA can exist either as a single molecule or in several pieces.  For example, both influenza virus and rotavirus have a segmented RNA genome.

4. influenza virus

5.  Almost all viruses contain only a single copy of their genome; ie, they are haploid.  The exception is the retrovirus family, whose members have two copies of their RNA genome; ie, they are diploid.

6. retrovirus

7. SIZE & SHAPE :  Viruses range from 20 to 300 nm in diameter.  This corresponds roughly to a range of sizes from that of the largest protein to that of the smallest cell.

8.  Spheres, rods, bullets, or bricks.  They are complex structures of precise geometric symmetry.  The shape of virus particles is determined by the arrangement of the repeating subunits that form the protein coat (capsid) of the virus.

9. VIRAL CAPSID & SYMMETRY :  The nucleic acid is surrounded by a protein coat called a capsid, made up of subunits called capsomers.  Each capsomer, consisting of one or several proteins.  The structure composed of the nucleic acid genome and the capsid proteins is called the nucleocapsid.

11.  arrangement of capsomers gives the virus structure its geometric symmetry.  Viral nucleocapsids have two forms of symmetry:  (1) icosahedral, in which the capsomers are arranged in 20 triangles that form a symmetric figure (an icosahedron) with the approximate outline of a sphere.  (2) helical, in which the capsomers are arranged in a hollow coil that appears rod- shaped. The helix can be either rigid or flexible.

14.  All human viruses that have a helical nucleocapsid are enclosed by an outer membrane called an envelope.  There are no naked helical viruses.  Viruses that have an icosahedral nudeocapsid can be either enveloped or naked.

16.  The advantage of building the virus particle from identical protein subunits is 2-fold: (1)it reduces the need for genetic information. (2)it promotes self- assembly; ie, no enzyme or energy is required. In fact, functional virus particles have been assembled in the test tube by combining the purified nucleic acid with the purified proteins in the absence of cells, energy source, and enzymes.

17.  The envelope is a lipoprotein membrane composed of : 1) lipid derived from the host cell membrane. 2)protein that is virus-specific. VIRAL ENVELOPE :  There are frequently glycoproteins in the form of spike- like projections on the surface, which attach to host cell receptors during the entry of the virus into the cell.  The matrix protein, mediates the interaction between the capsid proteins and the envelope.

19.  The viral envelope is acquired as the virus exits from the the cell in a process called "budding".  The envelope of most viruses is derived from the cell's outer membrane.  Exception of herpesviruses that derive their envelope from the cell's nuclear membrane.

20.  The presence of an envelope confers instability on the virus. Enveloped viruses are more sensitive to heat, drying, detergents, and lipid solvents such as alcohol and ether than are nonenveloped (nucleocapsid) viruses.  virtually all viruses that are transmitted by the fecal- oral route (those that have to survive in the environment) do not have an envelope.  These include viruses such as hepatitis A virus, poliovirus, coxsackievirus, echovirus, Norwalk virus, and rotavirus.

21.  In contrast, enveloped viruses are most often transmitted by direct contact, such as by blood or by sexual transmission.  Examples of these include human immunodeficiency virus, herpes simplex virus type 2, and hepatitis B and C viruses.  Other enveloped viruses are transmitted directly by insect bite, eg, yellow fever virus and West Nile virus, or by animal bite, eg, rabies virus.

22.  Many other enveloped viruses are transmitted from person to person in respiratory aerosol droplets, such as influenza virus, measles virus, rubella virus, respiratory syncytial virus, and varicella-zoster virus.  If the droplets do not infect directly, they can dry out in the environment, and these enveloped viruses are rapidly inactivated.  Rhinoviruses, which are transmitted by respiratory droplets, are naked nucleocapsid viruses and can survive in the environment for significant periods.

23.  Viral proteins serve several important functions:  The outer capsid proteins protect the genetic material.  mediate the attachment of the virus to specific receptors on the host cell surface. This interaction of the viral proteins with the cell receptor is the major determinant of species and organ specificity. VIRAL PROTEINS :

24.  Outer viral proteins are also important antigens.  Induce neutralizing antibody and activate cytotoxic T cells to kill virus-infected cells.  These outer viral proteins not only induce antibodies but are also the target of antibodies, ie, antibodies bind to these viral proteins and prevent ("neutralize") the virus from entering the cell and replicating.

25.  They are also the determinants of type specificity (often called the serotype ).  Some viruses produce antigenic variants of their surface proteins that allow the viruses to evade our host defenses.  For example, poliovirus types 1, 2, and 3 are distinguished by the antigenicity of their capsid proteins.  Antibody against one serotype will not protect against another serotype.

26.  It is important to know the number of serotypes of a virus, because vaccines should contain the prevalent serotypes. There is often little cross- protection between different serotypes.  Viruses that have multiple serotypes, ie, have antigenic variants, have an enhanced ability to evade our host defenses.

27.  The internal viral proteins are : 1)Structural : the capsid proteins of the enveloped viruses. 2)Enzymes : the polymerases that synthesize the viral mRNA.  The internal viral proteins vary depending on the virus.  Some viruses have a DNA or RNA polymerase attached to the genome; others do not.

28.  Some viruses produce proteins that act as " super- antigens".  Viruses known to produce superantigens include : 1)Two members of the herpesvirus family, namely, Epstein- Barr virus and cytomegalovirus. 2)The retrovirus mouse mammary tumor virus. The current hypothesis offered to explain why these viruses produce a super- antigen is that activation of CD4-positive T cells is required for replication of these viruses to occur.

29. ATYPICAL VIRUSLIKE AGENTS : There are four exceptions to the typical virus as de- scribed above: (1)Defective viruses :  are composed of viral nucleic acid and proteins but cannot replicate without a "helper" virus, which provides the missing function.  usually have a mutation or a deletion of part of their genetic material.

30.  Because these defective particles can interfere with the growth of the infectious particles, it has been hypothesized that the defective viruses may aid in recovery from an infection by limiting the ability of the infectious particles to grow.  During the growth of most human viruses, many more defective than infectious virus particles are produced.  The ratio of defective to infectious particles can be as high as 100:1.

31. (2 ) Pseudovirions :  Contain host cell DNA instead of viral DNA within the capsid.  They are formed during infection with certain viruses when the host cell DNA is fragmented and pieces of it are incorporated within the capsid protein.  Pseudovirions can infect cells, but they do not replicate.

32. (3) Viroids :  Consist solely of a single molecule of circular RNA without a protein coat or envelope.  The RNA is quite small and apparently does not code for any protein.  Nevertheless, viroids replicate but the mechanism is unclear.  They cause several plant diseases but are not implicated in any human disease.

33. (4) Prions :  Prions are infectious particles composed entirely of protein. They have no DNA or RNA.  They cause diseases such as Creutzfeldt-Jakob disease and kuru in humans and mad cow disease and scrapie in animals.  These diseases are called transmissible spongiform encephalopathies. The term spongiform refers to the sponge-like appearance of the brain seen in these diseases. The holes of the sponge are vacuoles resulting from dead neurons.

34.  Prions are composed of a single glycoprotein with a molecular weight of 27,000-30,000.  Prion proteins are encoded by a single cellular gene.  This gene is found in equal numbers in the cells of both infected and uninfected animals.  The amount of prion protein mRNA is the same in uninfected as in infected cells.

35.  In view of these findings, posttranslational modifications of the prion protein are hypothesized to be the important distinction between the protein found in infected and uninfected cells.  There is evidence that a change in the conformation from the normal alpha-helical form to the abnormal beta-pleated sheet form is the important modification.  The abnormal form then recruits additional normal forms to change their configuration, and the number of abnormal pathogenic particles increases.

36.  When these proteins are in the normal, alpha-helix configuration, they are nonpathogenic.  But when their configuration changes to a beta-pleated sheet, they aggregate into filaments, which disrupts neuronal function and results in the symptoms of disease.

37.  Prions are highly resistant to inactivation by ultraviolet light, heat, formaldehyde and nucleases.  They are inactivated by hypochlorite, NaOH, and autoclaving.  Because they are normal human proteins, they do not elicit an inflammatory response or an antibody response in humans.