Virology

 Virology 

Introduction

Virus:

Definition: A Virus is an infectious agent that is minimally constructed of two components: 

1) A genome consisting of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), but not both, and 

2) A protein-containing structure (capsid) designed to protect the genome

The other infectious agents like bacteria, fungi, protozoa, and worms, are either single cells or composed of many cells. Cells are capable of independent replication, can synthesize their own energy and proteins, and can be seen in the light microscope. In contrast, viruses are not cells; they are not capable of independent replication, can synthesize neither their own energy nor their own proteins, and are too small to be seen in the light microscope.

Terms & Definitions in Virology:

Capsid: The protein shell, or coat, that encloses the nucleic acid genome. 

Capsomeres: Morphologic units seen in the electron microscope on the surface of icosahedral virus particles. Capsomeres represent clusters of polypeptides, but the morphologic units do not necessarily correspond to the chemically defined structural units. 

Defective virus: A virus particle that is functionally deficient in some aspect of replication. 

Envelope: A lipid-containing membrane that surrounds some virus particles. It is acquired during viral maturation by a budding process through a cellular membrane. Virus-encoded glycoproteins are exposed on the surface of the envelope. These projections are called peplomers. 

Nucleocapsid: The protein-nucleic acid complex representing the packaged form of the viral genome. The term is commonly used in cases where the nucleocapsid is a substructure of a more complex virus particle.

Structural units: The basic protein building blocks of the coat. They are usually a collection of more than one nonidentical protein subunit. The structural unit is often referred to as a protomer. 

Subunit: A single folded viral polypeptide chain. 

Virion: The complete virus particle. In some instances (eg, papillomaviruses, picornaviruses), the virion is identical with the nucleocapsid. In more complex virions (herpesviruses, orthomyxoviruses), this includes the nucleocapsid plus a surrounding envelope. This structure, the virion, serves to transfer the viral nucleic acid from one cell to another. 

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. 

Viroids consist solely of a single molecule of circular RNA without a protein coat or envelope. There is extensive homology between bases in the viroid RNA, leading to large double-stranded regions. The RNA is quite small (MW 1 x 105) 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. 

Prions are infectious particles that are composed solely of protein; i.e., they contain no detectable nucleic acid. They are implicated as the cause of certain "slow" diseases called transmissible spongiform encephalopathies, which include such diseases as Creutzfeldt-Jakob disease in humans. Because neither DNA nor RNA has been detected in prions, they are clearly different from viruses.. Prions are much more resistant to inactivation by ultraviolet light and heat than are viruses. They are remarkably resistant to formaldehyde and nucleases. However, they are inactivated by hypochlorite, NaOH, and autoclaving. Hypochlorite is used to sterilize surgical instruments and other medical supplies that cannot be autoclaved. 

Important Properties of Viruses: 

1. Since viruses can’t make their own energy or synthesize important biomolecules like proteins, they are obligate intracellular parasites. 

2. Virus contains either DNA or RNA and not both. And it must have the information in its nucleic acids to self-assemble, since host cell doesn’t have that information. 

3. Viruses are non living and infectious in nature. 

Size of Virus: 

Size ranges from 20 nm (smallest virus; parvoviridae) to 400 nm (largest virus; pox viridae). 

Viruses cannot be seen through light microscope since it only allows a magnification of upto 10-6 of a meter (μm). But they can be visualized through electron microscope, which allows a magnification of upto 10-9 of a meter (nm). 

Shape of virus: 

Viruses may be different shapes like spherical, rod-shaped, brick-shaped, tad-pole shaped, bullet-shaped, or filamentous. 

Nucleocapsid shape is more important though. It could be 

a. Helical (flu, mumps, measles, rabies viruses), 

b. Cubic or icosahedral (Adenovirus, Human papilloma virus, CMV, Hepatitis A, B, C, E) or 

c. Complex; which is a complex of both cubic and helical (tailed T4 bacteriophage, Pox virus).

Pathogenesis:

The ability of viruses to cause disease can be viewed on two distinct levels: 

(1) the changes that occur within individual cells and 

(2) the process that takes place in the infected patient. 

- The Infected Cell:

Death of infected cells is probably caused by inhibition of cellular protein synthesis. Translation of viral mRNA into viral proteins preempts the ribosomes preventing synthesis of cellular proteins. 

Inclusion bodies are aggregates of virions in specific locations in the cell that are useful for laboratory diagnosis. Two important examples are Negri bodies in the cytoplasm of rabies virus-infected cells and owl's eye inclusions in the nucleus of cytomegalovirus-infected cells. 

Multinucleated giant cells form when cells are infected with certain viruses, notably herpesviruses and paramyxoviruses such as respiratory syncytial virus. 

Cytopathic effect (CPE) is a visual or functional change in infected cells typically associated with the death of cells. 

Malignant transformation occurs when cells are infected with oncogenic viruses. Transformed cells are capable of unrestrained growth. 

The Infected Patient:

Viral infection in the person typically has four stages: incubation period, prodromal period, specific-illness period, and recovery period. 

Most serious viral infection are systemic, i.e., the virus travels from the portal of entry via the blood to various organs. However, some are localized to the portal of entry, such as the common cold, which involves only the upper respiratory tract. 

Factors contributing to Pathogenesis of a viral infection:

The symptoms of viral diseases are usually caused by death of the infected cells and a consequent loss of function. For example, poliovirus kills neurons, resulting in paralysis. 

Immunopathogenesis is the process by which the symptoms of viral diseases are caused by the immune system rather than by the killing of cells directly by the virus. One type of immunopathogenesis is the killing of virus-infected cell by the attack of cytotoxic T cells that recognize viral antigens on the cell surface. Damage to the liver caused by hepatitis viruses occurs by this mechanism. Another is the formation of virus–antibody complexes that are deposited in tissues. Arthritis associated with parvovirus B19 or rubella virus infection occurs by this mechanism. 

Viruses can evade host defenses by producing multiple antigens, thereby avoiding inactivation by antibodies, and by reducing the synthesis of class I MHC proteins, thereby decreasing the ability of a cell to present viral antigens and blunting the ability of cytotoxic T cells to kill the virus-infected cells. Viruses also produce receptors for immune mediators, such as IL-1 and TNF, thereby preventing the ability of these mediators to activate antiviral processes. 

Persistent Viral Infections: 

Carrier state refers to people who produce virus for long periods of time and can serve as a source of infection for others. The carrier state that is frequently associated with hepatitis C virus infection is a medically important example. 

Latent infections are those infections that are not producing virus at the present time but can be reactivated at a subsequent time. The latent infections that are frequently associated with herpes simplex virus infection are a medically important example. 

Slow virus infections refer to those diseases with a long incubation period, often measured in years . Some, such as progressive multifocal leukoencephalopathy, are caused by viruses, whereas others, such as Creutzfeldt-Jakob disease, are caused by prions. The brain is often the main site of these diseases.