Skip to main content
Download PDF

Simon Litvak (1942–2022)

Retrovirology volume 19, Article number: 8 (2022) Cite this article

A talented Chilean-French biochemist, mentor to many brilliant students, with a unique scientific character, a friend who developed a strong collaborative research and teaching program between Chile and France.

Simon Litvak (Fig. 1) was born in the Chilean Coastal city and harbor of Valparaiso in 1942.

Fig. 1
figure 1

Simon Litvak a talented Chilean–French biochemist

Full size image

His initial focus was on protein synthesis in cell-free extracts, obtaining his professional degree in Biochemistry at the Faculty of chemistry and pharmacology of the University of Chile at Santiago (1965) [1, 2]. He then moved to Paris, France, to work under the supervision of François Chapeville on the biosynthesis of nucleic acids. Specifically, he worked on the 3′ end modification of the genomic RNA of the plant tymovirus Turnip yellow mosaic virus (TYMV), discovering that it was a substrate for the host enzyme tRNA nucleotidyltransferase, which added several nucleotides at the viral RNA 3′ end because the viral last 82 nucleotides folded into a tRNA-like structure [3, 4]. Along this line of research, Simon and collaborators found that the 3′ end domain of TYMV could be aminoacylated, causing a positive effect on the activity of the VIRAL REPLICASE [5]. He obtained his Ph.D. in Natural Sciences in 1972 from the University Paris VII. He then continued his work on the study of the interaction of viral RNAs and tRNA nucleotidyl transferases.

Investigating plant DNA polymerases and the viral reverse transcriptase

Soon after the discovery of reverse transcriptase in 1970, in 1975, Simon set up a research program on the plant DNA POLYMERASES [6,7,8]  and on the famous retroviral DNA POLYMERASE, later called Reverse Transcriptase (RT) of avian myeloblastosis virus (AMV) [9,10,11,12,12] and the human immunodeficiency virus HIV [13,14,15,16].

Interestingly enough, DNA POLYMERASE A of the wheat germ was found to be active on RNA templates, in other words, to exhibit a reverse transcriptase activity [17].

A large amount of work was dedicated to the AMV and HIV RTs. In both cases, RTs were found to bind to the homologous RT tRNA initiator primer, namely tRNATrip for AMV RT and tRNALYS for HIV in a specific manner [15]. His work showed the role of viral RTs in the selection and positioning of the tRNA primer on the viral genomic RNA [12,13,14, 16, 18] and proposing a mechanism by which the primer tRNA is packaged during virus assembly.

Studies on RNA editing in wheat germ mitochondria and HIV

RNA editing is a biochemical process whereby some residues of an RNA sequence can be deaminated, giving rise to a C to U transition. This editing process modifies the primary sequence of an mRNA having important consequences such as generating a stop or initiation codon [19,20,21,22,23,24]. To investigate in detail the editing process Simon and his group developed an original system based on wheat germ mitochondria. He also participated in studies showing that HIV-1 RNA could suffer C to U editing [25, 26]. His studies also extended to other HIV enzymes, such as the viral integrase IN [27,28,29,30,31].

France–Chile scientific cooperation

Simon Litvak established a strong French–Chile collaborative effort to develop the study of nucleic acids and viruses in Chile (Fig. 2). Since early in his career, he organized international courses and conferences in spectacular cities such as Pucon at the foot of the Villarica volcanoe in Chile. He was constantly bringing renowned international scientists in the fields of nucleic acids research and virology to Chile. This international program enabled young Chilean sciences to attend state-of-the-art lectures and directly interact with first-class scientists. Also, it allowed many young Chilean students to be offered unique opportunities to develop their scientific careers in Europe and North America under the supervision of top scientific mentors. Many of these brilliant young students returned to Chile to continue as independent scientists, reinforcing the study of nucleic acids and virology in the South-American countries.

Fig. 2
figure 2

Simon Litvak (left) and Marcelo López-Lastra at ENS Lyon, June the first 2011

Full size image

Publications of Simon Litvak cited (among 162 publications)

  1. Litvak S, Agosin M. Protein synthesis in polysomes from houseflies and the effect of DDT. Biochemistry. 1968;7:1560–7.

    Article  CAS  Google Scholar 

  2. Litvak S, Boeckx R, Dakshinamurti K. Identification of biocytin in biotin proteins using high voltage electrophoresis. Anal Biochem. 1969;30:470–547.

    Article  CAS  Google Scholar 

  3. Litvak S, Carré DS, Chapeville F. TYMV-RNA as a substrate of the tRNA nucleotidyl transferase. FEBS Lett. 1970;11:316–9.

    Article  CAS  Google Scholar 

  4. Litvak S, Tarrago-Litvak L, Chapeville F. TYMV-RNA as a substrate of the tRNA nucleotidyltransferase. II. Incorporation of CMP and determination of a short nucleotide sequence at the 3′ end of the RNA. J Viral. 1973;11:238–42.

    Article  CAS  Google Scholar 

  5. Litvak S, Tarrago A, Tarrago-Litvak L, Allende JE. Elongation factor-viral genome interaction dependent on the aminoacylation of TYMV and TMV RNAs. Nature. 1973;241:88–90.

    CAS  Google Scholar 

  6. Christophe L, Tarrago-Litvak L, Castroviejo M, Litvak S. Mitochondrial DNA polymerase from wheat embryos. Plant Sci Lett. 1981;21:181–92.

    Article  CAS  Google Scholar 

  7. Castroviejo M, Tarrago-Litvak L, Litvak S. Partial purification and characterization of two cytoplasmic DNA polymerases from ungerminated wheat. Nucleic Acids Res. 1975;2:2077–90.

    Article  CAS  Google Scholar 

  8. Tarrago-Litvak L, Castroviejo M, Litvak S. Studies on a DNA polymerase gamma-like from wheat embryos. FEBS Lett. 1975;59:125.

    Article  CAS  Google Scholar 

  9. Array A, Litvak S. Studies on the interaction of tRNA and avian myeloblastosis DNA polymerase. Cold Spring Harbor Symp Q B. 1979;43:631–7.

    Article  Google Scholar 

  10. Araya A, Sarih L, Litvak S. Reverse transcriptase mediated binding of primer tRNA to the viral genome. Nucleic Acids Res. 1979;6:3831–4384.

    Article  CAS  Google Scholar 

  11. Litvak S, Araya A. Primer tRNA in retroviruses. Trends Biochem Sci. 1982;7:361–4.

    Article  CAS  Google Scholar 

  12. Garret M, Romby P, Giégé R, Litvak S. Interactions between AMV reverse transcriptase and tRNATrp. Mapping of complexed tRNA with chemicals and nucleases. Nucleic Acids Res. 1984;12:2259–71.

    Article  CAS  Google Scholar 

  13. Sallafranque-Andreola M, Robert D, Barr PJ, Fournier M, Litvak S, Sarih-Cottin L, Tarrago-Litvak L. HIV reverse transcriptase expressed in transformed yeast cells. Biochemical properties and interactions with bovine tRNALys. Eur J Biochem. 1989;184:367–74.

    Article  CAS  Google Scholar 

  14. Robert D, Sallafranque-Andreola ML, Bordier B, Sarih-Cottin L, Tarrago-Litvak L, Graves PV, Barr PJ, Fournier M, Litvak S. Interactions with tRNALys induce important structural changes in HIV reverse transcriptase. FEBS Lett. 1990;277:239–42.

    Article  CAS  Google Scholar 

  15. Litvak S, Sarih-Cottin L, Fournier M, Andreola ML, Tarrago-Litvak L. Priming of HIV replication by tRNALys: role of reverse transcriptase. Trends Biochem Sci. 1994;19:114–8.

    Article  CAS  Google Scholar 

  16. Dufour E, Reinbolt J, Castroviejo M, Ehresmann B, Litvak S, Tarrago-Litvak L, Andreola ML. Cross-linking localization of a HIV-1 reverse transcriptase peptide involved in the binding of primer tRNALys3. J Mol Biol. 1999;285:1339–46.

    Article  CAS  Google Scholar 

  17. Laquel P, Sallafranque-Andreola ML, Tarrago-Litak L, Castroviejo M, Litvak S. Wheat embryo DNA polymerase A reverse transcribes natural and synthetic RNA templates. Biochemical characterization and comparison with animal DNA polymerase gamma and retroviral reverse transcriptase. Biochim Biophys Acta. 1990;1048:139–48.

    Article  CAS  Google Scholar 

  18. Sarih-Cottin L, Bordier B, Musier-Forsyth K, Andreola ML, Barr PJ, Litvak S. Preferential interaction of HIV RT with two regions of primer tRNALys as evidenced by footprinting studies and inhibition with synthetic oligoribonucleotides. J Mol Biol. 1992;226:1–6.

    Article  CAS  Google Scholar 

  19. Begu D, Graves PV, Domec C, Arselin G, Litvak S, Array A. RNA editing of wheat mitochondrial ATP synthase subunit 9: direct protein and cDNA sequencing. Plant Cell. 1990;2:1283–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Araya A, Domec C, Begu D, Litvak S. An in vitro system for the editing of ATP synthase subunit 9 mRNA using wheat mitochondrial extracts. Proc Natl Acad Sci USA. 1992;89:1040–4.

    Article  CAS  Google Scholar 

  21. Hernould M, Mouras A, Litvak S, Araya A. RNA editing of the mitochondrial atp9 transcrit from tobacco. Nucleic Acids Res. 1992;20:1809.

    Article  CAS  Google Scholar 

  22. Araya A, Begu D, Litvak S. RNA editing in plants. Physiol Plant. 1994;91:543–50.

    Article  CAS  Google Scholar 

  23. Blanc V, Litvak S, Araya A. RNA editing in wheat mitochondria proceeds by a deamination mechanism. FEBS Lett. 1995;373:56–60.

    Article  CAS  Google Scholar 

  24. Kurek I, Ezra D, Begu D, Erel N, Litvak S, Breiman A. Studies on the effects of nuclear background and tissue specificity on RNA editing of the mitochondrial ATP synthase subunits a, 6 and 9 in fertile and cytoplasmic male-sterile (CMS) wheat. Theor Appl Genet. 1997;95:1305–11.

    Article  CAS  Google Scholar 

  25. Bourara K, Litvak S, Araya A. Generation of G to A and C to U changes in HIV-1 transcripts by RNA editing. Science. 2000;289:1564–6.

    Article  CAS  Google Scholar 

  26. Freund F, Boulmé F, Litvak S, Tarrago-Litvak L. Initiation of HIV-2 reverse transcription: a secondary structure model of the RNA/tRNALys3 duplex. Nucl Acids Res. 2001;29:85–93.

    Article  Google Scholar 

  27. Parissi V, Calmels C, Richard de Soultrait V, Caumont A, Fournier M, Chaignepain S, Litvak S. Functional interactions of HIV-1 integrase with human and yeast HSP60. J Virol. 2001;75:11344–53.

    Article  CAS  Google Scholar 

  28. Tarrago-Litvak L, Andreola ML, Fournier M, Nevinsky G, Parissi V, Richard de Soultrait V, Litvak S. Inhibitors of HIV-1 reverse transcriptase and integrase: classical and emerging therapeutical approaches. (An invited review). Curr Pharm Des. 2002;8:595–614.

    Article  CAS  Google Scholar 

  29. Richard de Soultrait V, Caumont A, Parissi V, Morellet N, Ventura M, Lenoir C, Litvak S, Fournier M, Roques B. A novel short peptide is a specific inhibitor of the HIV-1 integrase. J Mol Biol. 2002;318:45–58.

    Article  Google Scholar 

  30. Bugreev DM, Baranova S, Zakharova OD, Parissi V, Desjobert C, Sottofattori E, Balbi A, Litvak S, Tarrago-Litvak L, Nevinsky GA. Dynamic, thermodynamic and kinetic basis for recognition and transformation of DNA by human immunodeficiency virus type 1 integrase. Biochemistry. 2003;42:9235–47.

    Article  CAS  Google Scholar 

  31. Desjobert C, de Soultrait VR, Faure A, Parissi V, Litvak S, Tarrago-Litvak L, Fournier M. Identification by phage display selection of a short peptide able to inhibit only the strand transfer reaction catalyzed by human immunodeficiency virus type 1 integrase. Biochemistry. 2004;43:13097–105.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratorio de Virología Molecular, Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile

    Marcelo López-Lastra

  2. MFP UMR 5234 Université de Bordeaux, 146 Rue Léo Saignat, 33076, Bordeaux Cedex, France

    Vincent Parissi

  3. UMR 7021 CNRS, Laboratoire de Bioimagerie et Pathologies, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France

    Jean-Luc Darlix

Authors
  1. Marcelo López-Lastra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent Parissi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean-Luc Darlix
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Marcelo López-Lastra or Jean-Luc Darlix.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

López-Lastra, M., Parissi, V. & Darlix, JL. Simon Litvak (1942–2022). Retrovirology 19, 8 (2022). https://doi.org/10.1186/s12977-022-00595-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/s12977-022-00595-3

Retrovirology

ISSN: 1742-4690

Contact us