Two Hundred Twenty Years of Landmark Discoveries.docx

8/22/2019 Two Hundred Twenty Years of Landmark Discoveries.docx

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TABLE 1. Two Hundred Twenty Years of Landmark Discoveries and Counting

Date Discovery

1796 Cowpox virus used to vaccinate against smallpox (Jenner)

1885 Rabies vaccine developed (Pasteur)1892 Description of filterable infectious agent (TMV) (Ivanovsky)

1898 Concept of the virus as a contagious living form (TMV) (Beijerinck)

First description of an animal virus (FMDV) (Loeffler, Frosch)

1901 First identification of avian influenza; fowl plague virus (Lode, Gruber)

1901 First description of a human virus (yellow fever virus) (Reed et al.)

1903 Rabies virus identified (Remlinger, Riffat-Bay); rabies inclusion bodies described (Negri)1908 Leukemia-causing virus identified (Ellerman, Bang)

1909 Poliovirus identified (Landsteiner, Popper)

1911 Discovery of solid tumor virus transmitted to chickens (RSV) (Rous)

1912 Tissue culture of a chicken embryo explants (Carrel)

1913 An early example of virus propagation in tissue culture (Steinhardt)

1915-17 First description of bacterial viruses (bacteriophages) (Twort, d'Herelle)1931 Virus propagation in embryonated chicken eggs (Woodruff, Goodpasture)

1931 Use of mice as a host for viruses (Furth)

1931 Identification of swine influenza virus (Shope)

1933 Identification of human influenza virus (Smith et al.)

1933 Identification of rabbit papilloma virus (Shope)


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1933 Mouse mammary tumors identified (Staff of the Jackson Memorial Laboratory)

1935 Tobacco mosaic virus crystallized (Stanley)

1936 Induction of carcinomas in other species by rabbit papillomavirus (Rous; Beard)

1938 Yellow fever vaccine (Thieler)1939 One-step growth cycle for phages (Ellis, Delbruck)

1941 Recognition of influenza virus hemagglutination (HA); HA inhibition by antibody. Discovery of

first virus-associated (receptor destroying enzyme, neuraminidase) enzyme (Hirst)

1946 Mixed bacteriophage infection leads to genetic recombination (Delbruck)

1947 Mutation and DNA repair in bacteriophages (multiplicity reactivation) (Luria)

1948 Poliovirus replication in nonneuronal cell culture (Enders, Weller, Robbins)1948 Culture of single animal cells (Sanford)

1952 Poliovirus plaque assay (Dulbecco)

1952 Bacteriophage genome is nucleic acid (Hershey, Chase)

1952 Transduction of genetic information (Zinder, Lederberg)

1952 Restriction and Modification of DNA (Luria)

1954 Polio vaccine developed (Salk)1955 Human single cell culture (HeLa) (Gey et al.)

1955 Optimization of cell growth medium (Eagle)

1955 Definition of a gene (cis-trans test) (Benzer)

1957 In vitro assembly of virus (TMV) (Fraenkel-Conrat, Williams)

1957 Discovery of interferon (Isaacs, Lindemann)


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1958 Bacteriophage lambda regulation paradigm (Pardee, Jacob, Monod)

1958 Definition of the episome (Jacob, Wollman)

1961 Discovery of messenger RNA (mRNA) using bacteriophages (Brenner, Jacob, Meselson)

1961 Elucidation of the triplet code by genetic analysis of bacteriophages (Crick et al.)1961 Genetic definition of nonsense codons as stop signals for translation in bacteriophages (Campbell,

Epstein, Bernstein)

1963 Discovery of hepatitis B virus (Blumberg)

1964 Colinearity of a bacteriophage gene with the polypeptide chain (Sarabhai, Stretton, Brenner)

Discovery of first human tumor virus, EBV (Epstein-Barr)

1966 Pathways of macromolecular assembly of bacteriophages (Edgar, Wood)1967 Phage repressor isolated (Ptashne)

1967 Description of viroids (Diener)

1970 Discovery of retroviral reverse transcriptase (Temin, Baltimore)

1972 Recombinant DNA technology phage and SV40 (Berg)

1973 Discovery that major histocompatibility complex (MHC) presents viral antigens to lymphocytes

(Doherty, Zinkernagel)

First restriction enzyme map of a viral genome, SV40 (Nathans)

1974 Phage lambda viral vectors for recombinant DNA technology (Murray, Davis, Blattner, Enquist)

1976 Retroviral oncogenes are derived from cells (Bishop, Varmus)

1977 RNA splicing discovered in adenovirus (Roberts, Sharp, Chow, Broker)


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1978 First viral genome sequenced (phiX174, Sanger)

1978 Virus crystal structure (TBSV) (Harrison)

1979 Discovery of the p53 tumor suppressor protein bound to the simian vacuolating virus 40 (SV40)

T-antigen (Levine, Lane)1979 World Health Organization declares smallpox eradicated

1981 Development of infectious recombinant clone for an RNA virus, poliovirus (Racaniello,

Baltimore)

1981 Structure of first viral envelope protein (Wiley, Skehel, Wilson)

1983 Description of human immunodeficiency virus (HIV) as causative agent of acquired

immunodeficiency syndrome (AIDS) (Montagnier, Gallo)1989 Hepatitis C virus cloned (Houghton et al.)

1990 Human gene therapy with a retrovirus vector

1994 Kaposi's sarcoma herpes virus discovered (HHV-8) (Chang, Moore)

1997 HAART treatment for AIDS

2003 Severe acute respiratory syndrome (SARS) outbreak and containment; rapid identification of

novel human coronavirus2005 Hepatitis C virus propagated in tissue culture (Chisari; Rice; Wakita)

2005 1918 influenza virus genome reconstructed and sequenced (Palese, Tumpey, Taubenberger)

TMV, tobacco mosaic virus; FMDV, foot and mouth disease virus; RSV, respiratory syncytial virus; TBSV,

tomato bushy stunt virus; HAART, highly active anti-retroviral therapy.


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Yesterday July 28, 2013

Herpes simplex virus 1 has an internal pressure eight times higher than a car tire, and uses it to literally blast its

DNA into human cells, according to a new study published online in the Journal of the Am er ican Chemical

Society.

Dr Alex Evilevitch and his colleagues provide the first

experimental evidence of a high internal pressure of tens

of atmospheres within Herpes simplex virus 1, resulting

from the confined genome. NPC nuclear pore complex

(Bauer DW et al)
http://pubs.acs.org/doi/abs/10.1021/ja404008rhttp://pubs.acs.org/doi/abs/10.1021/ja404008rhttp://pubs.acs.org/doi/abs/10.1021/ja404008rhttp://pubs.acs.org/doi/abs/10.1021/ja404008rhttp://pubs.acs.org/doi/abs/10.1021/ja404008rhttp://pubs.acs.org/doi/abs/10.1021/ja404008r


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The study provides the first experimental evidence of high internal pressure within a virus that infects humans a

phenomenon previously only attributed to viruses that infect bacteria.

Despite billions of years of evolution separating eukaryotic viruses and bacteriophages, the existe nce of an internal

pressure capable of powering the ejection of DNA into a host cell has been conserved. This suggests that it is a key

mechanism for viral infection across organisms and presents us with a new drug target for antiviral therapies, said DrAlex

Evilevitch of Carnegie Mellon University, senior author of the study published in the Journal of the American Chemical

Society.

Many viruses, whether they infect bacteria, plants or animals, are adept at packing long stretches of DNA or RNA within

their nanometer-sized protein shells.

Herpes simplex virus 1 (HSV-1) contains dsDNA that is 400 times longer than the radius of the viral shell it fills.

The DNA gets packaged so tightly that it bends upon itself, resulting in repulsive forces that exert tremendous energy and

pressure on the viruss outer shell. When HSV-1 infects a cell, it enters through the outer cell membrane and makes its

way to the cell nucleus, where it docks in a small hole found in the nuclear membrane. That act is like a key opening a lock

that allows the HSV-1 to eject its DNA into the cell nucleus.

For years, scientists hypothesized that a high internal pressure inside eukaryotic viruses like HSV-1 enabled the virus to

shoot its DNA into the host cells nucleus. But it was impossible to measure HSV-1s internal pressure without knowing

how to release the viral DNA in a controlled, experimental setting.


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Dr Evilevitchs colleagues Prof William Newcomb and Prof Jay Brown from the University of Virginias School of Medicine

discovered protein called UL6 that, when degraded, caused DNA to exit the virus.

In their experiments, they degraded UL6, which triggered HSV-1 to eject its DNA. At the same time, they applied an

external force to the virus and monitored how much DNA was released. When the external pressure reached tens of

atmospheres, HSV-1 didnt release any DNA, indicating that the internal and external pressure were equal.

This measurement of high internal pressure tens of atmospheres within a human virus is a fundamentally

important discovery of the physical-chemical mechanism of eukaryotic viral infection, Dr Evilevitch said.

The mechanism of pressurized infection found in HSV-1 is applicable to any of the eight known Herpes viruses that cause

disease in humans, including Varicella zoster virus, which causes chickenpox in children and shingles in adults, and the

Epstein-Barr virus, which causes mononucleosis and is associated with several types of cancer, such as Hodgkins

lymphoma.

Bibliographic information: Bauer DW et al. Herpes Virus Genome, The Pressure Is On. J. Am. Chem. Soc., published

online July 5, 2013; doi: 10.1021/ja404008r

http://www.sci-news.com/medicine/science-herpes-virus-dna-human-cells-01259.html
http://www.uniprot.org/uniprot/P10190http://www.sci-news.com/medicine/science-herpes-virus-dna-human-cells-01259.htmlhttp://www.sci-news.com/medicine/science-herpes-virus-dna-human-cells-01259.htmlhttp://www.sci-news.com/medicine/science-herpes-virus-dna-human-cells-01259.htmlhttp://www.uniprot.org/uniprot/P10190


8/17

Extremely Strange New Viruses Discovered

Thursday, July 25, 2013

A pair of startlingly unique viruses twice the size of the largest known viruses have beendiscoveredby a group of

French scientists. They have a shape similar to a container, and a completely novel set of genes inside, which

made their discoverers associate them with a Pandora's Box. Most of their genes are novel, and contain code that

does unknown things. There is some scientific speculation that these viruses are so unusual that they should be

thought of as a new life form entirely. The first, given the name Pandoravirus salinus, was found on sediment off

the coast of Las Cruces, Chile. The second, Pandoravirus dulcis, was was located in a pond near Melbourne,

Australia

Read the original source:

http://www.unknowncountry.com/news/extremely-strange-new-viruses-discovered#ixzz2aRBzR6PR
http://www.sciencemag.org/content/341/6143/226.summary?sid=10ee4cf8-5f92-4b3a-ab48-65d6a61b6ad1http://www.sciencemag.org/content/341/6143/226.summary?sid=10ee4cf8-5f92-4b3a-ab48-65d6a61b6ad1http://www.sciencemag.org/content/341/6143/226.summary?sid=10ee4cf8-5f92-4b3a-ab48-65d6a61b6ad1http://www.unknowncountry.com/news/extremely-strange-new-viruses-discovered#ixzz2aRBzR6PRhttp://www.unknowncountry.com/news/extremely-strange-new-viruses-discovered#ixzz2aRBzR6PRhttp://www.unknowncountry.com/news/extremely-strange-new-viruses-discovered#ixzz2aRBzR6PRhttp://www.sciencemag.org/content/341/6143/226.summary?sid=10ee4cf8-5f92-4b3a-ab48-65d6a61b6ad1


9/17

May 27, 2013

A new SARS-like virusrecently found in humans continues to spread -- with the worldwide total now at 49, the

World Health Organization said Wednesday.

Of the 49 known infections with the MERS-CoV virus, 27 have resulted in death, the organization said.

The latest deaths were reported in Saudi Arabia.

The Saudi health ministry said Wednesday that three people died from their infections in the country's eastern

region.

Health workers infected with coronavirus

How is dangerous new virus spreading?
http://www.who.int/csr/disease/coronavirus_infections/en/http://www.who.int/csr/disease/coronavirus_infections/en/http://www.who.int/csr/disease/coronavirus_infections/en/


10/17

WHO tracks new virus to Middle East

The virus is "a threat to the entire world," the WHO's general director said Monday.

It "is not a problem that any single affected country can keep to itself or manage all by itself," Margaret Chan said

Monday in her closing remarks at the 66th World Assembly in Geneva, Switzerland.

Although many of the cases have occurred on the Arabian Peninsula, people have died of the infection

elsewhere.

However, "all of the European cases have had a direct or indirect connection to the Middle East," the WHO said

earlier this month. But "in France and the United Kingdom, there has been limited local transmission among close

contacts who had not been to the Middle East but had been in contact with a traveler recently returned from the

Middle East."
http://www.who.int/csr/disease/coronavirus_infections/update_20130517/en/index.htmlhttp://www.who.int/csr/disease/coronavirus_infections/update_20130517/en/index.htmlhttp://www.who.int/csr/disease/coronavirus_infections/update_20130517/en/index.html


11/17

Virology in the 21st Century

TABLE 2. Landmarks in the study of virusesa

Era and year Landmark (virus or scientist)

Protovirology

1798 Cowpox lesions used to vaccinate against smallpox (Jenner)1882 Transmission of tobacco mosaic disease with cell-free extracts (Mayer)1885 Development of rabies vaccine (Pasteur, Roux)Auroravirology

1892 Description of filterable infectious agent (TMV) (Ivanovsky)1898 Development of concept of virus as contagious element (TMV) (Beijerinck)

Discovery of first animal virus (FMDV) (Loeffler, Frosch)

1901 Discovery of first human virus (yellow fever virus) (Reed)1903 Discovery of rabies virus (Remlinger, Riffat-Bay)1908 Discovery of first leukemia-causing virus (Ellerman, Bang)1909 Discovery of poliovirus (Landsteiner, Popper)

1911 Discovery of first solid tumor virus (RSV) (Rous)

Discovery of measles virus (Goldberger, Anderson)

1913 Virus cultivation in tissue culture (VV) (Steinhardt, Lambert)1915 Discovery of bacterial viruses (bacteriophages) (Twort, d'Hrelle)


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1917 Development of the plaque assay and discovery of the particulate nature of viruses(bacteriophage) (d'Hrelle)

1931 Propagation of virus in embryonated chicken eggs (Woodruff, Goodpasture)1932 Discovery of first mammalian tumor virus (MMTV) (Little, Bittner)1933 Discovery of human influenza virus (Smith)

Discovery of rabbit papillomavirus (Shope)

First description of viral mutants (TMV) (Jensen)

Meridiovirology

1934

Discovery that bacteriophages are composed of protein and nucleic acids (Schlesinger)1935 Crystallization of TMV (Stanley)

1938 Development of yellow fever vaccine (Theiler)

Use of electron microscopy for viruses (TMV) (von Borries, Ruska, Ruska)

1939 Description of one-step growth cycle (bacteriophage) (Ellis, Delbrck)1941 Discovery of first virus-associated enzymes (influenza virus) (Hirst)

1943 Discovery of genetic origins of mutations (bacteriophage) (Luria, Delbruck)1945 Development of influenza vaccine (Francis)1946 Discovery of genetic recombination by bacteriophage (Delbruck)

Replication of poliovirus in nonneuronal cell cultures (Enders, Weller, Robbins

Discovery of eclipse phase of virus infection (bacteriophage) (Doermann)

1951 Discovery of bacteriophage (E. Lederberg)


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Discovery that lysogenic phages produce diphtheria toxin (Freeman)

1952 Plaque assay of animal virus (poliovirus) (Dulbecco)

Discovery that viral genome is nucleic acid (Hershey, Chase)Transduction of genetic information by bacteriophage (Zinder, J. Lederberg)

1953 Discovery of host-controlled restriction and modification (Luria, Bertani, Weigle)1954 Development of polio vaccines (Salk, Sabin)1955 Culture of human cells (HeLa) (Gey)

Optimization of cell growth medium (Eagle)

Definition of a gene (cis-trans

test) (bacteriophage) (Benzer)In vitro assembly of infectious virus (TMV) (Fraenkel-Conrat, Williams)

Janovirology

1956 Discovery of mRNA in bacteriophage infection (Volkin, Astrachan, Brenner, Jacob, Meselson) Discovery that virus particles are composed of identical subunits (Watson, Crick)

Discovery that RNA can carry genetic information (TMV) (Schramm, Fraenkel-Conrat,

Williams)1957 Discovery of interferon (Isaacs, Lindemann)

Discovery of respiratory syncytial virus (Chanock)

1958 Discovery of bacteriophage regulation paradigm (Pardee, Jacob, Monod, Lwoff)

1960 Discovery of SV40 (Sweet and Hilleman)Demonstration of the triplet nature of the genetic code (bacteriophage) (Crick)


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Elucidation of nonsense codons (bacteriophage) (Campbell, Epstein, Bernstein)

1962 Studies of virus structure (Klug, Caspar)

1964 Demonstration of the colinearity of gene with polypeptide chain (bacteriophage) (Brenner) Discovery of first human tumor virus (EBV) (Epstein, Barr, Burkitt)

1965 Autocatalytic in vitro synthesis of bacteriophage DNA (Spiegelman)1966 Experimental transmission of spongiform encephalopathy to primates (kuru)

(Gajdusek, Gibbs, Hadlow)

1967 Discovery of hepatitis B virus (Blumberg)

Isolation of bacteriophage repressor (Ptashne)Discovery of viroids (Diener)

Discovery of first virion-associated polymerase (VV) (McAuslan, Kates)

1970 Discovery of retroviral reverse transcriptase (Temin, Baltimore)

1971 Discovery of RNA polyadenylation (Darnell, Edmonds)1972 Development of first recombinant DNA molecules (phage , SV40) (Berg)

Proposal that reassortment of influenza virus segments is the origin of pandemic strains(Webster, Laver)

1973 Development of first restriction map (SV40) (Nathans)

Discovery of major histocompatibility locus restriction of viral antigen recognition

(Doherty, Zinkernagel)

Discovery of human rotavirus (R. Bishop)


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1974 Development of first transgenic mouse (SV40) (Mintz)1975 Discovery of mRNA capping (Shatkin, Moss)Neovirology1976 First RNA virus genome sequenced (bacteriophage MS2) (Fiers)

Demonstration that retroviral oncogenes are derived from cells (J. M. Bishop, Varmus)

1977 First DNA virus genomes sequenced (X174, SV40) (Sanger, Fiers, Weissman) Discovery of RNA splicing (adenovirus) (Roberts, Sharp)

Discovery of tumor suppressor p53 (SV40) (Levine, Crawford)

Description of first virus crystal structure (TBSV) (Harrison)1978 Development of the first infectious molecular clone of an RNA virus (Qbeta, Weissmann)1979 Declaration of smallpox eradication by World Health Organization

First in vitro replication of eukaryotic viral DNA (adenovirus, SV40) (Kelly, Hurwitz, Stillman)

Development of first in vitro mRNA transcription system (adenovirus) (Roeder)

Discovery of first highly active, template-specific, RNA-dependent RNA polymerase from a

eukaryotic source (BMV) (Hall)Discovery of tyrosine kinases (Hunter, Erikson, Eckhart)

1980 Discovery of first human retrovirus (HTLV-1) (Gallo)1981 Development of first infectious molecular clones of an animal RNA virus (poliovirus)

(Baltimore)

Discovery of transcriptional enhancers (Chambon, Khoury, Schaffner)


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Development of hepatitis B virus vaccine

Identification of mammalian transcription factors (MMTV, SV40) (Yamamoto, Tjian)

Discovery of insertional activation of cellular oncogenes by retroviruses (Hayward, Astrin) Identification of polyadenylation signal (Shenk)

Discovery of the Cre/lox recombination system in phage P1 (Sternberg)

1982 Development of antiviral and other drugs (Elion, Hitchings)

Definition of prions (Prusiner)

1983 High-risk human papillomaviruses identified and linked to cervical cancer (zur Hausen)

Discovery of AIDS virus (HIV) (Montagnier, Barre-Sinoussi, Gallo)1984 Discovery of nuclear localization signals (Smith, Butel)

Production of first infectious, multicomponent virus from cloned DNA (BMV) (Ahlquist)

1986 Development of first recombinant viral vaccine (hepatitis B virus)Generation of transgenic virus-resistant plants (TMV) (Beachy)

Discovery of hammerhead ribozymes (TRSV, ASV) (Bruening, Symons)

1988

Discovery that DNA virus oncogene products bind cellular tumor suppressor proteins(adenovirus, SV40, HPV) (Harlow, Weinberg, Livingston, Howley)

Development of first ribozyme with engineered specificity (Haseloff)

Discovery of internal ribosome entry sites (poliovirus) (Wimmer, Sonenberg)

1989 Discovery of hepatitis C virus (Houghton)1990 Development of first human gene therapy with a retrovirus vector (Anderson, Blaese)


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1991 Discovery of viral antiapoptotic proteins (baculovirus) (Miller)1995 Development of HAART treatment for AIDS

1998 Discovery of gene silencing by double-stranded RNA, an antiviral response (Fire, Mello) Use of plant virion for synthesis of nanoparticles (Young)

Discovery that plant viruses encode suppressors of RNAi (Vance, Baulcombe)

2001 Discovery of the caveosome (SV40) (Helenius)2002 Worldwide outbreak and containment of SARS2005 Reconstruction and sequencing of the 1918 influenza virus genome (Palese, Garcia-Sastre,

Tumpey, Taubenberger)2006 Development of vaccine against human papillomavirus, the first vaccine designed to prevent

human cancer

aDiscoveries recognized by a Nobel prize are highlighted in bold. This list of landmarks in virology is not

comprehensive. We apologize to the many colleagues whose important contributions could not be included because of

space and time constraints. Abbreviations: ASV, avocado sunblotch viroid; BMV, brome mosaic virus; EBV, Epstein-

Barr virus; HAART, highly active antiretroviral therapy; HPV, human papillomavirus; HTLV, human T-cell leukemia

virus; MMTV, mouse mammary tumor virus; RNAi, RNA interference; RSV, Rous sarcoma virus; TBSV, tomato bushy

stunt virus; TMV, tobacco mosaic virus; TRSV, tobacco ringspot virus; VV, vaccinia virus.
http://jvi.asm.org/content/83/11/5296/T2.expansion.html#xref-fn-4-1http://jvi.asm.org/content/83/11/5296/T2.expansion.html#xref-fn-4-1

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