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Fundamentals of Viral Biology

Post by on Saturday, July 10, 2021

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Viruses are essentially nonliving repositories of nucleic acid that require the presence of a living prokaryotic or eukaryotic cell for the replication of the nucleic acid. There are a number of different viruses that challenge the human immune system and that may produce disease in humans. In general, a virus is a small, infectious agent that consists of a core of genetic material (either deoxyribonucleic acid [DNA] or ribonucleic acid [RNA]) surrounded by a shell of protein. All viruses share the need for a host in order to replicate their deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). The virus commandeers the host’s existing molecules for the nucleic acid replication process. There are a number of different viruses. The differences include the disease symptoms they cause, their antigenic composition, type of nucleic acid residing in the virus particle, the way the nucleic acid is arranged, the shape of the virus, and the fate of the replicated DNA. These differences are used to classify the viruses and have often been the basis on which the various types of viruses were named. 
Virology, viral classification, types of viruses
Virology is the discipline of microbiology that is concerned with the study of viruses. Viruses can exist in a variety of hosts. Viruses can infect animals (including humans), plants, fungi, birds, aquatic organisms, protozoa, bacteria, and insects. Some viruses are able to infect several of these hosts, while other viruses are exclusive to one host. 
The classification of viruses operates by use of the same structure that governs the classification of bacteria. The International Committee on Taxonomy of Viruses established the viral classification scheme in 1966. From the broadest to the narrowest level of classification, the viral scheme is: Order, Family, Subfamily, Genus, Species, and Strain/type. To use an example, the virus that was responsible for an outbreak of Ebola hemorrhagic fever in a region of Africa called Kikwit is classified as Order Mononegavirales, Family Filoviridae, Genus Filovirus, and Species Ebola virus Zaire. 
In the viral classification scheme, all families end in the suffix viridae, for example Picornaviridae. Genera have the suffix virus. For example, in the family Picornaviridae there are five genera: enterovirus, cardio virus, rhinovirus, apthovirus, and hepatovirus. The names of the genera typically derive from the preferred location of the virus in the body (for those viral genera that infect humans). As examples, rhinovirus is localized in the nasal and throat passages, and hepatovirus is localized in the liver. Finally, within each genera there can be several species. 
There are a number of criteria by which members of one grouping of viruses can be distinguished from those in another group. For the purposes of classification, however, three criteria are paramount. These criteria are the host organism or organisms that the virus utilizes, the shape of the virus particle, and the type and arrangement of the viral nucleic acid. 
An important means of classifying viruses concerns the type and arrangement of nucleic acid in the virus particle. Some viruses have two strands of DNA, analogous to the double helix of DNA that is present in prokaryotes such as bacteria and in eukaryotic cells. Some viruses, such as the Adenoviruses, replicate in the nucleus of the host using the replication machinery of the host. 
An aspect of virology is the identification of viruses. Often, the diagnosis of a viral illness relies, at least initially, on the visual detection of the virus. For this analysis, samples are prepared for electron microscopy using a technique called negative staining, which highlights surface detail of the virus particles. For this analysis, the shape of the virus is an important feature. A particular virus will have a particular shape. For example, viruses that specifically infect bacteria, the so-called bacteriophages, look similar to the Apollo lunar lander (LEM spacecraft). A head region containing the nucleic acid is supported on a number of spiderlike legs. Upon encountering a suitable bacterial surface, the virus acts like a syringe, to introduce the nucleic acid into the cytoplasm of the bacterium. 
Other viruses have different shapes. These include spheres, ovals, worm-like forms, and even irregular (pleomorphic) arrangements. Some viruses, such as the influenza virus, have projections sticking out from the surface of the virus. These are crucial to the infectious process. 
As new species of eukaryotic and prokaryotic organisms are discovered, no doubt the list of viral species will continue to grow. 
Viral genetics
Viral genetics, the study of the genetic mechanisms that operate during the life cycle of viruses, utilizes biophysical, biological, and genetic analyses to study the viral genome and its variation. The virus genome consists of only one type of nucleic acid, which could be a single or double stranded DNA or RNA. Single stranded RNA viruses could contain positive- sense (+RNA), which serves directly as mRNA or negative- sense RNA (−RNA) that must use an RNA polymerase to synthesize a complementary positive strand to serve as mRNA. Viruses are obligate parasites that are completely dependent on the host cell for the replication and transcription of their genomes as well as the translation of the mRNA transcripts into proteins. 
Viral proteins usually have a structural function, making up a shell around the genome, but may contain some enzymes that are necessary for the virus replication and life cycle in the host cell. Both bacterial virus (bacteriophages) and animal viruses play an important role as tools in molecular and cellular biology research. Virus genetics is studied by either investigating genome mutations or exchange of genetic material during the life cycle of the virus. The frequency and types of genetic variations in the virus are influenced by the nature of the viral genome and its structure
Virus replication
Viral replication refers to the means by which virus particles make new copies of themselves. Although precise mechanisms vary, viruses cause disease by infecting a host cell and commandeering the host cell’s synthetic capabilities to produce more viruses. The newly made viruses then leave the host cell, sometimes killing it in the process, and proceed to infect other cells within the host. 
Viruses cannot replicate by themselves. They require the participation of the replication equipment of the host cell that they infect in order to replicate. The molecular means by which this replication takes place varies, de- pending upon the type of virus. Viral replication can be divided up into three phases: initiation, replication, and release. 
The initiation phase occurs when the virus particle attaches to the surface of the host cell, penetrates into the cell and undergoes a process known as uncoating, where the viral genetic material is released from the virus into the host cell’s cytoplasm. The attachment typically involves the recognition of some host surface molecules by a corresponding molecule on the surface of the virus. These two molecules can associate tightly with one another, binding the virus particle to the surface. 
A virus particle may have more than one receptor molecule, to permit the recognition of different host molecules, or of different regions of a single host molecule. The molecules on the host surface that are recognized tend to be those that are known as glycoproteins. For example, the human immunodeficiency virus recognizes a host glycoprotein called CD4. Cells lacking CD4 cannot, for example, bind the HIV particle. For animal viruses, the uncoating phase is also referred to as the eclipse phase. No infectious virus particles can be detected during that 10 to 12 hour period of time. 
Replication of the viral material can be a complicated process, with different stretches of the genetic material being transcribed simultaneously, with some of these gene products required for the transcription of other viral genes. Also replication can occur along a straight stretch of DNA, or when the DNA is circular (the so-called “rolling circle” form). RNA-containing viruses must also undergo a reverse transcription from DNA to RNA prior to packaging of the genetic material into the new virus particles. 
In the final stage, the viral particles are assembled and exit the host cell. The assembly process can involve helper proteins, made by the virus or the host. These are also called chaperones. Other viruses, such as tobacco mosaic virus, do not need these helper chaperones, as the proteins that form the building blocks of the new particles spontaneously self-assemble. In most cases, the assembly of viruses is symmetrical; that is, the structure is the same throughout the viral particle. 
Release of viruses can occur by a process called budding. A membrane “bleb” containing the virus particle is formed at the surface of the cell and is pinched off. For herpes virus this is in fact how the viral membrane is acquired. In other words, the viral membrane is a host- derived membrane. Other viruses, such as bacteriophage, may burst the host cell, spewing out the many progeny virus particles. But many viruses do not adopt such a host destructive process, as it limits the time of an infection due to destruction of the host cells needed for future replication. 
An understanding of the fundamentals of virus structure, genetics, and replication is critical to virologists and other forensic investigators attempting to identify potential biogenic pathogens that may be exploited as agents in biological warfare or by bioterrorists. 
(Excerpt from: Peter Richman ‘Evolution of Virology: An Overview’)

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