Molecular virology

Last updated January 15, 2022

Molecular virology is the study of viruses on a molecular level. Viruses are submicroscopic parasites that replicate inside host cells.^[1]^[2] They are able to successfully infect and parasitize all kinds of life forms- from microorganisms to plants and animals- and as a result viruses have more biological diversity than the rest of the bacterial, plant, and animal kingdoms combined.^[2]^[3] Studying this diversity is the key to a better understanding of how viruses interact with their hosts, replicate inside them, and cause diseases.^[2]

Viral replication

Viruses rely on their host to replicate and multiply. This is because viruses are unable to go through cell division, as they are acellular–meaning they lack the genetic information that encode the necessary tools for protein synthesis or generation of metabolic energy; hence they rely on their host to replicate and multiply. Using the host cell's machinery the virus generates copies of its genome and produces new viruses for the survival of its kind and the infection of new hosts. The viral replication process varies depending on the virus's genome.^[2]

Classification

In 1971 David Baltimore, a Nobel Prize-winning biologist, created a system called Baltimore Classification System.According to this system, viruses are classified into seven classes based on their replication strategy:^[2]^[4]

Class I: Double-stranded DNA. Depending on the location of genome replication, this class can be subdivided into two groups: (a) viruses in which replication happens exclusively in the nucleus and is thus relatively dependent on cellular factors; (b) viruses replicating in cytoplasm that are mostly independent of cellular machinery due to the fact that they have acquired all needed factors for their genome's transcription and replication.^[2]
Class II: Single-stranded DNA. These viruses only replicate in the nucleus. A double-stranded intermediate is formed during the replication process that serves as a template for the synthesis of virus's single-stranded DNA.^[2]
Class III: Double-stranded RNA. The viruses in this class have segmented genomes. Each segment is transcribed individually to produce a monochromatic mRNA that codes for only one protein.^[2]
Class IV: Single-stranded RNA - Positive-sense. The genome of these viruses are positive-sense RNAs, in which the RNA is directly translated into a viral protein. These viruses can be subdivided into two groups depending on their translation process: (a) viruses with polycistronic mRNA, in which the RNA translates into multiple protein products; (b) viruses with more complex transcription than the first group where either subgenomic RNAs or two rounds of translation are necessary to produce the genomic RNA.^[2]
Class V: Single-stranded RNA - Negative-sense. All viruses in this class have negative-sense RNAs, in which the RNA complements mRNA, transcribes into a positive-sense RNA via a viral polymerase, and translates into viral protein. The viruses in this class either have segmented or unsegmented RNA; either way, replication occurs within the cell's cytoplasm.^[2]
Class VI: Single-stranded positive-sense RNA with DNA intermediate. These viruses use reverse transcriptase to convert the positive-sense RNA ( as the template) into DNA. Retroviruses are the most well-known family among this class.^[2]
Class VII: Double-stranded DNA with RNA intermediate. The genome of these viruses are gapped, double-stranded, and subsequently become filled to form cccDNA (covalently closed circular DNA). This group also use the reverse transcription during the process of maturation.^[2]

Replication cycle

Regardless of the differences among viral species, they all share six basic replication stages:^[2]^[5]

Attachment is the cycle's starting point and consists of specific bindings between anti-receptors (or virus-attachment proteins) and cellular receptors molecules such as (glyco)proteins. The host range of a virus is determined by the specificity of the binding. The attachment causes the viral protein to change its configuration and thus fuse with the host's cell membrane; thereby enabling the virus to enter the cell.^[6]

Penetration of virus happens either through membrane fusion or receptor-mediated endocytosis and leads to viral entry. Due to their rigid cellulose-made

(chitin in case of fungal cells) cell walls, plants and fungal cells get infected differently than animal cells. Often, a cell wall trauma is required for the virus to enter the cell.^[6]

Uncoating is the removal of viral capsid, which makes the viral nucleic acids available for transcription. The capsid could have been degraded by either host or viral enzymes, releasing the viral genome into the cell.^[6]

Replication is the multiplication of virus's genetic material. The process includes the transcription of mRNA, synthesis, and assembly of viral proteins and is regulated by protein expression.^[6]

Assembly process involves putting together and modifying newly made viral nucleic acids and structural proteins to form the virus's nucleocapsid.^[2]^[7]

Release of viruses could be done by two different mechanisms depending on the type of virus. Lytic viruses burst the cell's membrane or wall through a process called lysis in order to release themselves. On the other hand, enveloped viruses become released by a process called budding in which a virus obtain its lipid membrane as it buds out of the cell through membrane or intracellular vesicle. Both lysis and budding processes are highly damaging to the cell, with the exception of retroviruses, and often result in the cell's death.^[2]^[6]

Viral pathogenesis

Pathogenicity is the ability of one organism to cause disease in another. There is a specialized field of study in virology called viral pathogenesis in which it studies how viruses infect their hosts at the molecular and cellular level.^[2]

In order for the viral disease to develop several steps need to be taken. First, the virus has to enter the body and implant itself into a tissue ( e.g. respiratory tissue). Second, the virus has to reproduce extracellular after invading in order to make ample copies of itself. Third, the synthesized viruses must spread throughout the body via circulatory systems or nerve cells.^[8]

With regards to viral diseases it is essential to look at two aspects: (a) the direct effect of virus replication; (b) the body's responses to infection. The course and severity of all viral infections are determined by the dynamic between the virus and the host. Common symptoms of virus infections are fever, body aches, inflammation, and skin rashes. Most of these symptoms are caused by our immune system's response to infection and are not the direct effect of viral replication.^[2]

Cytopathic effects of virus

Often it is possible to recognize virus-infected cells through a number of common phenotypic changes referred to as cytopathis effects. These changes include:^[2]

Altered shape: The shape of adherent cells– cells that attach themselves to other cells or artificial substrates— may change from flat to round. In addition, the cell's extensions resembling tendrils – involved in cell's mobility and attachments—are withdrawn into the cell.^[2]
Detachment from the substrate: Happens as a result of adherent cells' damage. The cell damage is due to partial degradation of cytoskeleton.^[2]
Lysis: In this case the entire cell breaks down because of the absorption of extracellular fluid and swelling. Not all viruses cause lysis.^[2]
Membrane fusion: The adjacent cells' membranes fuse together and produce a mass called syncytium, in which the cytoplasm contains more than one nucleus and appears as a giant cell. These cells have a short lifespan compared to other cells.^[2]
Increase in Membrane permeability: Viruses can increase the membrane permeability which allows many extracellular ions( e.g. iodine and sodium ions) to enter the cell.^[2]

Viral infections

There are five different types of viral infections:^[2]

Abortive infection: This kind of infection occurs when a virus successfully invades a host cell but is unable to complete its full replication cycle and produce more infectious viruses.^[2]

Acute infection: Many common viral infections fallow this pattern. Acute infections are brief since they are often completely eliminated by the immune system. Acute infection is frequently associated with epidemics since most of virus replication happens before the onset of symptoms.^[2]
Chronic infection: These infections have a prolonged course and are hard to eliminate since the virus stays in the host for a significant period.^[2]
Persistent infection: There is a delicate balance between the host and the virus in this pattern. The virus adjusts its replication and pathogenecitiy levels to keep the host alive for its own benefit. While it is possible for the virus to live and replicate inside the host for its entire lifetime, oftentimes the host eventually eliminates the virus.^[2]
Latent infection: Being the ultimate infection, the latent virus infections tend to exist inside the host for its entire lifetime. A well-known example of such infection is the herpes simplex virus in humans. This virus is able to stop its replication and restrict its gene expression in order to stop the recognition of the infected cell by the host's immune system.^[2]

Prevention and treatment

Viral vaccines contain inactivated viruses which have lost their ability to replicate. These vaccines can prevent or lower the intensity of viral illness. Developing vaccines against smallpox, polio, and hepatitis B over the past 50 years has had a significant impact on world health and thus on global population. Nevertheless, there have been ongoing viral outbreaks ( such as the Ebola and Zika viruses) in the past few years affecting millions of people all around the globe.^[9] Therefore, more advanced understanding of molecular virology and viruses are needed for the development of new vaccines and the control of ongoing/future viral outbreaks.^[2]

An alternative way to treat viral infections would be antiviral drugs in which the drug blocks the virus's replication cycle. The specificity of an antiviral drug is the key to its success. These drugs are toxic to both the virus and the host but in order to minimize their damage they are developed in such a way as to be more toxic to the virus than to the host. The efficiency of an antiviral drug is measured by the chemotherapeutic index, given by:^[2]

{\frac {\hbox{Dose of drug that inhibits virus replication}}{\hbox{Dose of drug that is toxic to host}}}

The higher the drug's efficiency, the smaller the value of chemotherapeutic index. In clinical practice, this index is used to produce a safe and clinically useful drug.^[2]

Related Research Articles

A retrovirus is a type of virus that inserts a copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus.

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit its development.

Paramyxoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has four subfamilies, 17 genera, and 78 species, three genera of which are unassigned to a subfamily.

The lytic cycle is one of the two cycles of viral reproduction, the other being the lysogenic cycle. The lytic cycle results in the destruction of the infected cell and its membrane. Bacteriophages that only use the lytic cycle are called virulent phages.

Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm.

Φ6 is the best-studied bacteriophage of the virus family Cystoviridae. It infects Pseudomonas bacteria. It has a three-part, segmented, double-stranded RNA genome, totalling ~13.5 kb in length. Φ6 and its relatives have a lipid membrane around their nucleocapsid, a rare trait among bacteriophages. It is a lytic phage, though under certain circumstances has been observed to display a delay in lysis which may be described as a "carrier state".

Pestivirus is a genus of viruses, in the family Flaviviridae. Viruses in the genus Pestivirus infect mammals, including members of the family Bovidae and the family Suidae. There are 11 species in this genus. Diseases associated with this genus include: hemorrhagic syndromes, abortion, and fatal mucosal disease.

Baltimore classification Virus classification system made by David Baltimore

Baltimore classification is a system used to classify viruses based on their manner of messenger RNA (mRNA) synthesis. By organizing viruses based on their manner of mRNA production, it is possible to study viruses that behave similarly as a distinct group. Seven Baltimore groups are described that take into consideration whether the viral genome is made of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), whether the genome is single- or double-stranded, and whether the sense of a single-stranded RNA genome is positive or negative.

The murine leukemia viruses are retroviruses named for their ability to cause cancer in murine (mouse) hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses. Replicating MLVs have a positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA intermediate via the process of reverse transcription.

Molluscum contagiosum virus (MCV) is a DNA poxvirus that causes the human skin infection molluscum contagiosum. Molluscum contagiosum affects about 200,000 people a year, about 1% of all diagnosed skin diseases. Diagnosis is based on the size and shape of the skin lesions and can be confirmed with a biopsy, as the virus cannot be routinely cultured. Molluscum contagiosum virus is the only species in the genus Molluscipoxvirus. MCV is a member of the subfamily Chordopoxvirinae of family Poxviridae. Other commonly known viruses that reside in the subfamily Chordopoxvirinae are variola virus and monkeypox virus.

Phycodnaviridae is a family of large (100–560 kb) double-stranded DNA viruses that infect marine or freshwater eukaryotic algae. Viruses within this family have a similar morphology, with an icosahedral capsid. As of 2014, there were 33 species in this family, divided among 6 genera. This family belongs to a super-group of large viruses known as nucleocytoplasmic large DNA viruses. Evidence was published in 2014 suggesting that specific strains of Phycodnaviridae might infect humans rather than just algal species, as was previously believed. Most genera under this family enter the host cell by cell receptor endocytosis and replicate in the nucleus. Phycodnaviridae play important ecological roles by regulating the growth and productivity of their algal hosts. Algal species such Heterosigma akashiwo and the genus Chrysochromulina can form dense blooms which can be damaging to fisheries, resulting in losses in the aquaculture industry. Heterosigma akashiwo virus (HaV) has been suggested for use as a microbial agent to prevent the recurrence of toxic red tides produced by this algal species. Phycodnaviridae cause death and lysis of freshwater and marine algal species, liberating organic carbon, nitrogen and phosphorus into the water, providing nutrients for the microbial loop.

Double-stranded RNA viruses Type of virus according to Baltimore classification

Double-stranded RNA viruses are a polyphyletic group of viruses that have double-stranded genomes made of ribonucleic acid. The double-stranded genome is used to transcribe a positive-strand RNA by the viral RNA-dependent RNA polymerase (RdRp). The positive-strand RNA may be used as messenger RNA (mRNA) which can be translated into viral proteins by the host cell's ribosomes. The positive-strand RNA can also be replicated by the RdRp to create a new double-stranded viral genome.

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 9,000 virus species have been described in detail of the millions of types of viruses in the environment. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. The study of viruses is known as virology, a subspeciality of microbiology.

Plectrovirus is a genus of viruses, in the family Plectroviridae. Bacteria in the phylum Tenericutes serve as natural hosts, making these viruses bacteriophages. Acholeplasma virus L51 is the only species in the genus.

Adenovirus genomes are linear, non-segmented double-stranded (ds) DNA molecules that are typically 26-46 Kbp long, containing 23-46 protein-coding genes. The example used for the following description is Human adenovirus E, a mastadenovirus with a 36 Kbp genome containing 38 protein-coding genes. While the precise number and identity of genes varies among adenoviruses, the basic principles of genome organization and the functions of most of the genes described in this article are shared among all adenoviruses.

Batai orthobunyavirus (BATV) is a RNA virus belonging to order Bunyavirales, genus Orthobunyavirus.

This glossary of virology is a list of definitions of terms and concepts used in virology, the study of viruses, particularly in the description of viruses and their actions. Related fields include microbiology, molecular biology, and genetics.

Positive-strand RNA viruses are a group of related viruses that have positive-sense, single-stranded genomes made of ribonucleic acid. The positive-sense genome can act as messenger RNA (mRNA) and can be directly translated into viral proteins by the host cell's ribosomes. Positive-strand RNA viruses encode an RNA-dependent RNA polymerase (RdRp) which is used during replication of the genome to synthesize a negative-sense antigenome that is then used as a template to create a new positive-sense viral genome.

HSV epigenetics is the epigenetic modification of herpes simplex virus (HSV) genetic code.

The woolly monkey hepatitis B virus (WMHBV) is a viral species of the Orthohepadnavirus genus of the Hepadnaviridae family. Its natural host is the woolly monkey (Lagothrix), an inhabitant of South America categorized as a New World primate. WMHBV, like other hepatitis viruses, infects the hepatocytes, or liver cells, of its host organism. It can cause hepatitis, liver necrosis, cirrhosis, and hepatocellular carcinoma. Because nearly all species of Lagothrix are threatened or endangered, researching and developing a vaccine and/or treatment for WMHBV is important for the protection of the whole woolly monkey genus.

References

↑ Crawford, Dorothy (2011). Viruses: A Very Short Introduction. New york, NY: Oxford University Press. pp. 4–7. ISBN 978-0199574858.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 Cann, Alan (2012). Principles of Molecular Virology. ELSEVIER. p. 214. ISBN 9780123849403.
↑ Koonin, Eugene V.; Senkevich, Tatiana G.; Dolja, Valerian V. (1 January 2006). "The ancient Virus World and evolution of cells". Biology Direct. 1: 29. doi:10.1186/1745-6150-1-29. ISSN 1745-6150. PMC 1594570 . PMID 16984643.
↑ Dimmock, Nigel (2007). Introduction to Modern Virology. Wiley-Blackwell. ISBN 978-1-119-97810-7.
↑ Collier, Leslie; Balows, Albert; Sussman, Max (1998) Topley and Wilson's Microbiology and Microbial Infections ninth edition, Volume 1, Virology, volume editors: Mahy, Brian and Collier, Leslie. Arnold. ISBN 0-340-66316-2.
1 2 3 4 5 Dimmock, N.J; Easton, Andrew J; Leppard, Keith (2007) Introduction to Modern Virology sixth edition, Blackwell Publishing, ISBN 1-4051-3645-6.
↑ Barman, S; Ali, A; Hui, EK; Adhikary, L; Nayak, DP (2001). "Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses". Virus Res. 77 (1): 61–9. doi:10.1016/S0168-1702(01)00266-0. PMID 11451488.
↑ Baron, S (1996). Medical Microbiology Chapter 45 Viral Pathogenesis. Galveston (TX).
↑ "2014 Ebola Virus Disease Outbreak in West Africa". WHO. 21 April 2014.

Additional links

molecular biology
phage, the virus of bacteria/prokaryotes
viral plaque
Important publications in virology
Virus classification

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[1] Crawford, Dorothy (2011). Viruses: A Very Short Introduction. New york, NY: Oxford University Press. pp. 4–7. ISBN 978-0199574858.

[:1-2] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 Cann, Alan (2012). Principles of Molecular Virology. ELSEVIER. p. 214. ISBN 9780123849403.

[3] Koonin, Eugene V.; Senkevich, Tatiana G.; Dolja, Valerian V. (1 January 2006). "The ancient Virus World and evolution of cells". Biology Direct. 1: 29. doi:10.1186/1745-6150-1-29. ISSN 1745-6150. PMC 1594570 . PMID 16984643.

[4] Dimmock, Nigel (2007). Introduction to Modern Virology. Wiley-Blackwell. ISBN 978-1-119-97810-7.

[5] Collier, Leslie; Balows, Albert; Sussman, Max (1998) Topley and Wilson's Microbiology and Microbial Infections ninth edition, Volume 1, Virology, volume editors: Mahy, Brian and Collier, Leslie. Arnold. ISBN 0-340-66316-2.

[:0-6] 1 2 3 4 5 Dimmock, N.J; Easton, Andrew J; Leppard, Keith (2007) Introduction to Modern Virology sixth edition, Blackwell Publishing, ISBN 1-4051-3645-6.

[7] Barman, S; Ali, A; Hui, EK; Adhikary, L; Nayak, DP (2001). "Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses". Virus Res. 77 (1): 61–9. doi:10.1016/S0168-1702(01)00266-0. PMID 11451488.

[8] Baron, S (1996). Medical Microbiology Chapter 45 Viral Pathogenesis. Galveston (TX).

[9] "2014 Ebola Virus Disease Outbreak in West Africa". WHO. 21 April 2014.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]