Viruses

Published on 02/03/2015 by admin

Filed under Basic Science

Last modified 02/03/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 5581 times

Viruses

WHY YOU NEED TO KNOW

HISTORY

Submicroscopic particles were suspected when mummies with smallpox facial lesions, as well as scattered hieroglyphic accounts of inoculations against these killers, were discovered. Finally, later reports by Edward Jenner—and the milkmaid Sarah Nelmes—of successful vaccinations in the late eighteenth century culminated with the World Health Organization (WHO)-certified eradication of smallpox in 1979. This history suggested an organism smaller than visible bacteria.

Pathogenic microorganisms too small to be seen via light microscopy prompted a Dutch botanist-microbiologist, Martinus Willem Beijerinck (1851–1931), to coin the term virus (from the Latin virus, meaning toxin, poison). During this same time period (the late nineteenth century) Charles Chamberland made a porcelain filter for isolating these submicroscopic viruses. The tobacco mosaic virus was used in some of the first studies with these filters. The size of the filtered viruses was shown to be several orders of magnitude less than that of bacteria. Dimitri Ivanovski published experiments demonstrating the retained infectious nature of the filterable viral disease-causing agents, after bacteria had been removed by the filtration. Moreover, in the early 1900s, bacteria were even shown to be vulnerable to viral attack by bacteriophages. In 1935, the tobacco mosaic virus was crystallized by Wendell Stanley and identified as a mostly proteinaceous substance, shortly after which time it was further isolated into protein and nucleic acid constituents.

IMPACT

As expected, improved resolution with the advent of electron microscopy afforded the first visible records of viruses. Coupled with advances in biotechnology, the chemical nature of viral composition began to be deciphered, and with it new approaches to viral threats of various magnitudes could be explored. Filterable viruses yielded new functional explanations, and allowed their study for therapy. Diseases such as polio, influenza, AIDS, and rabies are now more accessible to laboratory study, leading to possible treatments to attenuate their effects before human exposure (antibiotics, although effective against bacteria, unfortunately are ineffective against viruses). The invention of the electron microscope made viruses visible and allowed the study of their response to putative chemical therapies or vaccinations.

FUTURE

Once the nature of a virus is visualized, biotechnological approaches via synthetic chemistry, genetic engineering, and computer-assisted screening of designed chemicals can be expeditiously undertaken (see New Drugs in Chapter 21, Pharmacology). These approaches can be applied to improve and test current therapies in use, as well as to develop and test new therapeutic and preventive substances. The complete identification of a virus and its virulence factors will help to design novel approaches to therapy and vaccination against future viral threats.

General Structure and Classification

Viruses are microscopic particles that infect cells of other organisms. They differ from other microorganisms in their structure, biology, and reproduction. Viruses do carry conventional genetic material in the form of DNA or RNA, but they cannot reproduce on their own because they lack the biochemical machinery necessary for replication. Viruses therefore are obligate intracellular parasites capable of infecting both eukaryotic and prokaryotic organisms. A virus that infects bacteria is referred to as a bacteriophage or simply phage. For a virus to reproduce, the individual components of the virus must be synthesized by the host cell and then assembled within that cell. In other words, a virus uses the biochemical machinery of its host cell in order to replicate.

Classification

To this date, taxonomic classification of viruses remains difficult because of the lack of fossil records and the ongoing debate about whether they should be considered living or nonliving organisms. At present, virus classification is based mainly on morphology, nucleic acid type, mode of replication, host organisms, and the type of disease they cause.

The International Committee on Taxonomy of Viruses (ICTV) is responsible for the development of the current viral classification system. In the early 1990s they devised and implemented rules for the naming and classification of viruses. This system shares several features with the classification system of cellular organisms, such as taxon structure. On the basis of shared properties, the viruses are grouped at the hierarchical levels of order, family, subfamily, genus, and species. The following latinized suffixes are given in italics within the taxon:

 Order (-virales)

  Family (-viridae)

   Subfamily (-virinae)

    Genus (-virus)

     Species (-virus)

For the determination of order, the type of nucleic acid DNA or RNA, single or double stranded, and the presence or absence of an envelope are used. In addition, other characteristics such as the type of host, the capsid shape, immunological properties, and the type of disease the virus causes are also considered for further detailed virus classification. An additional classification system is the Baltimore classification system, devised by David Baltimore. This system places the virus into one of seven groups distinguishing the viruses on the basis of the relationship between the viral genome and the messenger RNA (Box 7.1). In modern virus classification the ICTV system is used in conjunction with the Baltimore classification system. Although animal and plant virologists both use these systems, the actual application in the process of classification is quite different because of the diversity of viruses.

BOX 7.1   Baltimore Classification of Viruses

Group I: Double-stranded DNA (dsDNA) viruses

Group II: Single-stranded DNA (ssDNA) viruses

Group III: Double-stranded RNA (dsRNA) viruses

Group IV: Positive-sense single-stranded RNA [(+)ssRNA] viruses

Group V: Negative-sense single-stranded RNA [(−)ssRNA] viruses

Group VI: Reverse-transcribing diploid single-stranded RNA (ssRNA-RT) viruses

Group VII: Reverse-transcribing circular double-stranded DNA (dsDNA-RT) viruses

HEALTHCARE APPLICATION
Medically Important Viruses

Family Genus (or Subfamily) Species or Typical Member Infection/Disease
DNA Viruses
Parvoviridae Erythrovirus B19 virus Erythema infectiosum
Papillomaviridae Papillomavirus Human papillomavirus (HPV) More than 60 HPV types: common warts, plantar warts, flat cutaneous warts, etc.
Polyomaviridae Polyomavirus Polyomavirus

Adenoviridae Mastadenovirus Human adenovirus 2 Gastrointestinal tract infections, infection of the conjunctiva, central nervous system infections, urinary tract infections Herpesviridae Alphaherpesvirinae

  Varicellovirus Varicella-zoster virus (human herpesvirus 3 [HHV-3]) Chickenpox and shingles   Gammaherpesvirinae   Betaherpesvirinae Cytomegalovirus (HHV-5) Infectious mononucleosis, retinitis, etc.   Roseolovirus Roseolovirus (HHV-6, -7) Sixth disease (roseola infantum or exanthema subitum) Poxviridae Orthopoxvirus   Parapoxvirus Oral virus Cutaneous lesions   Molluscipoxvirus Molluscum contagiosum virus Wartlike skin lesions Hepadnaviridae Orthohepadnavirus Hepatitis B virus Hepatitis B RNA Viruses Picornaviridae Enterovirus Poliovirus Poliomyelitis   Rhinovirus Human rhinovirus A Common cold   Hepatovirus Hepatitis A virus Hepatitis A   Aphthovirus Foot-and-mouth disease virus Foot-and-mouth disease Caliciviridae Calicivirus Norovirus Gastroenteritis Astroviridae Astrovirus Human astroviruses (five serotypes) Gastroenteritis Togaviridae Alphavirus Sindbis virus Sindbis virus disease, polyarthritis and rash     Ross River virus Epidemic polyarthritis     Chikungunya virus Fever, petechial or maculopapular rash (limbs and trunk), arthralgia or arthritis   Rubivirus Rubella virus Rubella Flaviviridae Flavivirus Yellow fever virus Yellow fever     Dengue virus Dengue hemorrhagic fever     Tick-borne encephalitis viurs Encephalitis   Hepatitis C viruses Hepatitis C virus Hepatitis C Reoviridae Reovirus Reoviruses 1–3 Gastrointestinal and respiratory infections   Rotavirus Human rotavirus A, B, and C Gastrointestinal infections   Orbivirus Colorado tick fever virus Colorado tick fever (Mountain tick fever) Orthomyxoviridae Influenzavirus A, B Influenza A and B Influenza   Influenza C Influenza C virus Influenza Paramyxoviridae Paramyxovirus Newcastle disease virus Zoonotic: Parainfluenza (influenza-like)   Morbillivirus Measles virus (rubeola virus) Measles   Rubulavirus Mumps virus Mumps   Pneumovirus Respiratory syncytial virus Respiratory tract infections Rhabdoviridae Vesiculovirus Vesicular stomatitis virus Influenza-like symptoms; malaise, nausea, pain in limbs and back, possible vesicular lesions in mouth, lips and hands, leukopenia   Lyssavirus Rabies virus Rabies Bunyaviridae Bunyavirus Various arthropod-transmitted diseases   Hantavirus Hantavirus, Puumala virus, Seoul virus Hemorrhagic fever with renal syndrome   Nairovirus Crimean-Congo hemorrhagic fever virus Crimean-Congo hemorrhagic fever

image

Morphology

The size of viruses varies from very small, such as the parvovirus at about 20 nm and the poliovirus at 30 nm, to fairly large, such as the vaccinia virus at 400 nm and the poxviruses, which can be up to 450 nm. Most viruses cannot be visualized by light microscopy; therefore electron microscopy is used to examine their structure (see Chapter 1, Scope of Microbiology). However, some viruses are as large as or larger than the smallest bacteria and can be visualized by high optical magnification (Figure 7.1).

An exception to the size of other viruses is a virus discovered in 2003 by a team of French researchers, which named the organism mimivirus. This virus was found in free-living amoebas and has a diameter of 750 nm, which is larger than a Mycoplasma bacterium. These organisms also have the largest known viral genome, with about 1000 genes on a double-stranded circular DNA. Mimivirus seems to be an icosahedral particle with a diameter of 400 nm, no envelope, and surrounded by 80-nm fibrils.

Viruses consist of genetic material carried in a “shell” called the viral coat or capsid. The capsid consists of proteins that are coded by the viral genome. The capsid is a complex and highly organized entity that gives form to the virus and serves as the basis for morphological distinction. Subunits referred to as protomeres assemble to form capsomeres, which in turn spontaneously aggregate to form the capsid. Proteins associated with nucleic acids are called nucleoproteins and the association of viral capsid proteins with viral nucleic acid is referred to as a nucleocapsid. At the junction points of the capsomeres, long projections from the nucleocapsids, called spikes, are frequently attached (Figure 7.2). These spikes aid in attachment to the host cell membrane receptors. Some viruses have an envelope around the coat and once the virus is fully assembled it is called a virion. Depending on the presence or absence of an envelope, viruses are referred to as naked or enveloped viruses (Figure 7.3).

According to the shape and arrangement of capsomeres and the presence of an envelope, viruses can be classified into four distinct morphological types:

Helical Viruses

Helical capsids have rod-shaped capsomeres, connected along their long axis, resembling a wide ribbon stacked around a central axis forming a helical structure with a central cavity, a hollow tube. As a result, these virions are rod shaped or filamentous and can be short and highly rigid, as in many plant viruses, or long and very flexible, as in many animal viruses. The genetic material can be single-stranded RNA (ssRNA) or single-stranded DNA (ssDNA) and is bound into the protein helix by the interactions between the negative charge on the nucleic acid and the positive charge on the proteins. The nucleocapsid of a naked helical virus is rigid and tightly wound into a cylinder-shaped structure. An example is the well-studied tobacco mosaic virus, an ssRNA virus that infects primarily tobacco plants and other members of the Solanaceae family (Figure 7.4). Enveloped helical nucleocapsids are more flexible and this type is found in several human viruses such as influenza and measles viruses.

Icosahedral Viruses

Capsids of many virus families are multifaced structures known as icosahedrons. These are three-dimensional, geometric figures with 12 corners, 20 triangular faces, and 30 edges (Figure 7.5). This icosahedral capsid symmetry results in a spherical appearance of viruses at low magnification. The arrangement of the capsomeres varies between the viruses and the shape and dimension of the icosahedron depend on the characteristics of its protomeres. Although the basic symmetry of icosahedral viruses is the same there are major variations in the number of capsomeres, and therefore differences in the size of the viruses. The basic triangular face of a small virus is constructed of 3 protomeres, with 60 of these subunits forming the whole capsid. For example, the poliovirus has 32 capsomeres, whereas an adenovirus has 240 capsomeres. During the assembling of an icosahedral virus the nucleic acid is packed into the center, forming a nucleocapsid. Icosahedral viruses can be naked, such as the adenovirus, or enveloped, as the herpes simplex virus (Figure 7.6). Included in this morphological group are the Iridoviridae (infect mainly invertebrates), Herpesviridae, Adenoviridae, Papovaviridae, and Parvoviridae.

Enveloped Viruses

Many viruses have an outer structure, the viral envelope, which surrounds the nucleocapsid. Enveloped viruses typically obtain their envelope by budding though a host plasma membrane (see Plasma Membrane in Chapter 3, Cell Structure and Function) but may also include some viral glycoproteins. In some cases the viral envelope is derived from other membranes in the host cell, such as from the membranes of the endoplasmic reticulum or the nuclear membrane. The creation of the viral envelope through the budding process allows the viral particles to leave the host cell without disrupting the plasma membrane and therefore without killing the cell. As a result, some budding viruses can set up persistent infections.

During the formation of the envelope some or all of the host membrane proteins are replaced by viral proteins and some form a layer between the capsid and the envelope. These envelope proteins are glycoproteins; they are exposed to the outside of the envelope as spikes. The lipid bilayer of the envelope is exclusively host specific whereas the majority or all of the glycoproteins are virus specific. The glycoproteins on the surface of the envelope serve to identify and bind to receptor sites on the plasma membrane of the host. Parts of the viral capsid and/or envelope are also responsible for stimulating the immune system of the host to produce antibodies that can neutralize the virus and prevent further infection (see Chapter 20, The Immune System). The viral envelope can give a virion protection from certain enzymes and chemicals; however, because enveloped viruses depend on their intact envelope to be infectious, agents that damage the envelope, such as alcohol and detergents, greatly reduce the infectivity of the virus (see Chapter 19, Physical and Chemical Methods of Control). An example of an enveloped virus is the influenza virus shown in Figure 7.7.