AN INTRODUCTION TO MICROBIOLOGY, VIROLOGY AND THE BIRTH OF COVID-19 (by Nakul Ravi)

Introduction to microbiology: 

Microbiology is the study of unicellular, acellular or multicellular microorganisms. Microbiology encompasses numerous sub-disciplines including virology, parasitology, mycology, protozoology, phycology, and bacteriology [1]. Microbiologists often rely on molecular biology tools such as DNA sequence-based identification and specialize in culture preparation and staining, isolation, and classification of microbial species with appropriate technique etc[2]. 


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History of microbiology:

In 1676, Antonie van Leeuwenhoek observed bacteria and other microorganisms using a single-lens microscope of his own design.  He is considered as the Father of microbiology as he was the first to use a simple, single-lensed microscope of his own design and observed microorganisms for the first time.


The field of bacteriology was founded in the 19th century by Ferdinand Cohn, a botanist who studied algae and photosynthetic bacteria which led him to describe several bacteria including Bacillus and Beggiatoa.

Louis Pasteur is most famous for his series of experiments designed to disprove the then widely held theory of spontaneous generation, thereby solidifying microbiology's identity as a biological science [3]. One of his students, Adrien Certes is considered to be the founder of marine microbiology. He is considered to be the father of microbiology. Koch is best known for his contributions to the germ theory of disease, proving that specific diseases were caused by specific pathogenic microorganisms. He developed a series of criteria that have become known as Koch's postulates. He is considered to be the Father of medical microbiology [3].

Beijerinck made two major contributions to microbiology: The discovery of viruses and the development of enrichment culture techniques. French-Canadian microbiologist, Felix d'Herelle, co-discovered bacteriophages in 1917 and was one of the earliest applied microbiologists. Joseph Lister was the first to use phenol disinfectant on the open wounds of patients.

In 2005, Marshall and Warren jointly proved that Helicobacter pylorus causes stomach ulcers.

Applications of microbiology:

Many microbes are also responsible for various beneficiary processes like industrial fermentation of alcohol, vinegar, and dairy products, antibiotic production and also act as molecular vehicles to transfer DNA to complex organisms such as plants and animals [4,5]. 
Scientists have also used microbes to produce biotechnologically important enzymes like Taq polymerase from Thermus aquaticus for PCR (Polymerase Chain Reaction) [6]. A variety of biopolymers, like polyesters, polysaccharides and polyamides, are produced by microorganisms. Microorganisms are used for the production of numerous biopolymers with custom properties suitable for medical applications such as tissue engineering and drug delivery.
They are also used for the biosynthesis of xanthan, alginate, cellulose, cyanophycin, poly (gamma-glutamic acid), levan, hyaluronic acid, organic acids, oligosaccharides, polysaccharides, and polyhydroxyalkanoates [5].

Virology:

Virology is the study of viral, microscopic, parasitic particles of genetic material contained in a protein coat. Virology is considered to be a subfield of microbiology and medicine that is it’s a sub-discipline [7].

Viruses can be classified according to the host cell they infect animal viruses, plant viruses, fungal viruses, and bacteriophages (viruses infecting bacterium, which includes the most complex viruses) [8].

It focuses on the following aspects of viruses:

           Viral structure.

           Classification of viruses.

           Evolution of viruses.

           Their pathology.

           Their property to utilize host cells for reproduction.

           Their interaction with the host organism’s physiology                       and immunity.

           The diseases caused by them.

           The techniques to isolate and culture them.

           Their use in research and therapy.

Viruses can be classified according to the host cell they infect animal viruses, plant viruses, fungal viruses, and bacteriophages (viruses infecting bacterium, which includes the most complex viruses) [9].

Another classification uses the geometrical shape of their capsid or the virus's structure (like the presence or absence of a lipid envelope). Viruses range in size from about 30 nm to about 450 nm, which means that most of them cannot be seen with light microscopes. The shape and structure of viruses have been elucidated by electron microscopy, NMR spectroscopy, and X-ray crystallography [8,9].

The most useful classification system distinguishes viruses according to the type of nucleic acid they use as genetic material and the viral replication method they employ to lure host cells into producing more viruses:

DNA viruses (double-stranded DNA viruses and single-stranded DNA viruses).

RNA viruses (positive-sense single-stranded RNA viruses, negative-sense single-stranded RNA viruses, and double-stranded RNA viruses).

Reverse transcribing viruses (double-stranded and single-stranded reverse-transcribing RNA viruses including retroviruses) [9].

One main motivation for the study of viruses is the fact that they cause many important infectious diseases, such as common cold, influenza, rabies, measles, diarrhoea, hepatitis, Dengue fever, yellow fever, polio, smallpox, and AIDS.

When the immune system of vertebrates encounters a virus, it may produce specific antibodies that bind to the virus and neutralize its infectivity or mark it for destruction. Antibody presence in blood serum is often used to determine whether a person has been exposed to a given virus in the past, with tests such as ELISA.

Vaccinations protect against viral diseases, in part, by eliciting the production of antibodies. Monoclonal antibodies, specific to the virus, are also used for detection, as in fluorescence microscopy.

The study of the manner in which viruses cause disease is viral pathogenesis. The degree to which a virus causes the disease is its virulence.

RNA interference, an important cellular mechanism found in plants, animals, and many other eukaryotes, most likely evolved as a defence against viruses. Elaborate machinery of interacting enzymes detects double-stranded RNA molecules and then proceeds to destroy all single-stranded versions of those detected RNA molecules [9].

Molecular biology and viral therapy:

Bacteriophages can be grown easily as viral plaques on bacterial cultures. They occasionally move genetic material from one bacterial cell to another in a process known as transduction and this horizontal gene transfer is one of the major reasons they served as a major research tool in the development of molecular biology [10].

The genetic code, the function of ribozymes, the first recombinant DNA and early genetic libraries were all arrived at using bacteriophages. Certain genetic elements derived from viruses, like highly effective promoters. Since some viruses that infect eukaryotes need to transport their genetic material into the host cell's nucleus, they are attractive tools for introducing new genes into the host. Modified retroviruses are often used for this purpose, as they integrate their genes into the host's chromosomes.

History of virology [11]:

The word virus appeared in 1599 and originally meant "venom". In 1796 Edward Jenner developed a safer method, using cowpox to successfully immunize a young boy against smallpox, and this practice was widely adopted.

Vaccinations against other viral diseases followed, including the successful rabies vaccination by Louis Pasteur in 1886. The nature of viruses, however, was not clear to these researchers.

In 1892, the Russian biologist Dmitry Ivanovsky used a Chamberland Filter to isolate the bacteria that caused tobacco mosaic disease. His experiments showed that crushed leaf extracts from infected tobacco plants remained infectious after filtration.

In 1898 Martinus Beijerinck repeated Ivanovski's work but went further and passed the "filterable agent" from plant to plant and concluded it infectious—replicating in the host—and thus was not a mere toxin. He called it “contagium vivum fluidum”.

In 1926 it was shown that scarlet fever is caused by a bacterium that is infected by a certain bacteriophage.

The Tobacco Mosaic Virus was the first virus that could be crystallized and whose structure was discussed elaborately. In 1963, the Hepatitis B virus was discovered by Baruch Blumberg who went on to develop a Hepatitis B vaccine.

In 1965, Howard Temin described the first retrovirus: a virus whose RNA genome was reverse transcribed into complementary DNA (cDNA), then integrated into the host's genome and expressed from that template.

The viral enzyme reverse transcriptase, which along with integrase is a distinguishing trait of retroviruses, was first described in 1970, independently by Howard Temin and David Baltimore.

The first retrovirus infecting humans was identified by Robert Gallo in 1974. Later it was found that reverse transcriptase is not specific to retroviruses; retrotransposons which code for reverse transcriptase are abundant in the genomes of all eukaryotes.

In 1975 the functioning of oncoviruses was clarified considerably. Until that time, it was thought that these viruses carried certain genes called oncogenes which, when inserted into the host's genome, would cause cancer.

A worldwide vaccination campaign led by the UN World Health Organization resulted in the eradication of smallpox in 1979.

In 1982, Stanley Prusiner discovered prions and showed that they cause scrapie. [12]

The first cases of AIDS were reported in 1981, and HIV, the retrovirus causing it, was identified in 1983 by Luc Montagnier, Françoise Barré-Sinoussi and Robert Gallo.

By 1985, Harald zur Hausen had shown that two strains of Human papillomavirus (HPV) cause most cases of cervical cancer. Two vaccines against these strains were released in 2006.

The first human studies attempted to correct the genetic disease severe combined immune deficiency (SCID), but clinical success was limited.

In 2002 it was reported that poliovirus had been synthetically assembled in the laboratory, representing the first synthetic organism. [12]

The strain of Influenza A virus subtype H1N1 that killed up to 50 million people during the Spanish flu pandemic in 1918 was reconstructed in 2005. The 2009 flu pandemic involved another strain of Influenza A H1N1, commonly known as "swine flu".

In 2008, Sputnik virophage was described, the first known virophage: it uses the machinery of a helper virus to reproduce and inhibits the reproduction of that helper virus. Sputnik reproduces in amoeba infected by mamavirus, a relative of the mimivirus mentioned above and the largest known virus to date.

Coronavirus:

Coronaviruses are a group of viruses that cause diseases in mammals and birds. Coronaviruses were discovered in the 1960s. In humans, the virus causes respiratory infections which are typically mild but, in rare cases, can be lethal. In cows and pigs, they may cause diarrhoea, while in chickens it can cause an upper respiratory disease. There are no vaccines or antiviral drugs that are approved for prevention or treatment.

The earliest ones discovered were infectious bronchitis virus in chickens and two viruses from the nasal cavities of human patients with the common cold.

Coronaviruses are believed to cause a significant percentage of all common colds in human adults and children. Coronaviruses cause colds with major symptoms like fever, pneumonia, bronchitis, etc in humans primarily in the winter and early spring. The much-publicized human coronavirus discovered in 2003, SARS-CoV which causes severe acute respiratory syndrome (SARS), has unique pathogenesis because it causes both upper and lower respiratory tract infections [13].

There are seven strains of human coronaviruses:

    1. Human coronavirus 229E (HCoV-229E).

    2. Human coronavirus OC43 (HCoV-OC43).

    3. SARS-CoV.

    4. Human coronavirus NL63 (HCoV-NL63, New Haven                     coronavirus)

    5. Human coronavirus HKU1

    6. Middle East respiratory syndrome coronavirus (MERS-CoV), previously referred to as HCoV-EMC.

    7. Novel coronavirus (2019-nCoV) also referred to as Wuhan pneumonia or Wuhan coronavirus.

Novel coronavirus:

A new coronavirus designated 2019-nCoV was identified in Wuhan, Hubei province, China after people developed pneumonia without a clear cause and for which existing vaccines or treatments were not effective.

The virus has shown evidence of human-to-human transmission and its transmission rate appeared to escalate in mid-January 2020, with several countries other than China reporting cases. The incubation period of the virus is between 2 and 14 days and it remains contagious during this time.

As of 6 February 2020, 28,359 cases have been confirmed by the Chinese government and as of 6 February 2020, 565 deaths have been attributed to the virus since the first confirmed death on 9 January, with 1,387 recoveries.[14]

The virus was first detected in Wuhan city, Central China, in December 2019. It is believed to have originated from wild animals, passing to humans thanks to the wildlife trade and wet markets. The virus spread to other Chinese provinces in early and mid-January 2020, helped by the Chinese New Year migration.


       

 (Image A- Cumulative confirmed cases by country, as of 23 June 2021)

 


(Image B- Symptoms of the virus)

            The virus was soon carried to other countries by international travellers:

    • Thailand (13 January);
    • Japan (15 January);
    • South Korea, Taiwan and the United States (20, 21 and 21 January);
    • Hong Kong, Macau and Singapore (22, 22 and 23 January);
    • France, Nepal, and Vietnam (24 January);
    • Australia and Malaysia (25 January);
    • Canada (26 January);
    • Germany (28 January);
    • Finland, Sri Lanka and the United Arab Emirates (29 January);
    • India, Italy and the Philippines (30 January);
    • The United Kingdom, Russ Russia, Sweden and Spain (31 January);
    • Belgium (4 February). [15]

    The WHO has published several testing protocols for 2019-nCoV. Testing uses real-time reverse transcription-polymerase chain reaction (rRT-PCR). This test can be done on respiratory or blood samples. Results are generally available within a few hours to days using the RT-PCR test.

By: R. Nakul

https://replicoo.blogspot.com/2021/06/stem-cell-therapy-for-corona-patients.html

https://replicoo.blogspot.com/2021/07/spyder-python-install.html

References:

[1]- https://microbiologysociety.org/why-microbiology-matters/what-is-microbiology.html
[2]- https://microbiologyonline.org/about-microbiology
[3]- Microbiology: Principles and Explorations-JACQUELYN and LAURA BLACK-John Wiley and Sons, INC- 8th Edition- Chapter 1: Scope and History of Microbiology- Page 19.
[4]- https://www.microscopemaster.com/microbiology.html
[5]- https://madhavuniversity.edu.in/applications-of-microbiology.html
[6]- Class XII NCERT Biology- Chapter 11 and 12
[7]- https://jvi.asm.org/content/83/11/5296
[8]- https://www.icgeb.org/science/infectious-diseases/virology/
[9]- Principles of Virology, Fourth Edition, DOI: 10.1128/9781555819521
[10]- https://www.uk-cpi.com/blog/how-science-is-using-viruses-to-make-you-better
[11]- https://www.sciencedirect.com/topics/medicine-and-dentistry/history-of-virology
[12]- https://www.rndsystems.com/resources/posters/significant-events-history-virology
[13]- https://www.medicalnewstoday.com/articles/256521.php
[14]- https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200127-sitrep-7-2019--ncov.pdf
[15]- https://www.cdc.gov/coronavirus/2019-ncov/index.html
A (Image) - https://en.wikipedia.org/wiki/2019%E2%80%9320_Wuhan_coronavirus_outbreak
B (Image) - https://en.wikipedia.org/wiki/2019%E2%80%9320_Wuhan_coronavirus_outbreak


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