DEPARTMENT OF VIRUS-CELL INTERACTION
Vadim Izrailevich Agol
The Department was organized in 1965, and is headed until present, by Prof.
V. I.Agol.
The Department includes Laboratory of molecular epidemiology (
Head: PhD G.Yu. Lipskaya). Among staff members and graduate students working
in the Department during different period of times – G.A.Belov, E.A.Cherkasova,
I.M.Chumakov, K.M.Chumakov, V.A.Ginevskaya, A.P.Gmyl, A,E,Gorbalenya, T.M.Dmitrieva,
E.V.Koonin, T.V.Pestova, E.V.Pilipenko, Yu.V.Svitkin, T.G.Senkevich, T.Yu.Ugaroiva.
Major research advances: Working out of the first cell-free
system for efficient synthesis and processing of picornavirus proteins [Svitkin
et al., 1978]. Identification of a protease (now called 3C) involved in this
processing [Gorbalenya et al., 1979; Svitkin et al., 1979]. Characterization
of structure-function relationships in the translational cis-elements of
picornaviral RNAs [Pilipenko et al., 1989; 1989a; 1992; 1994; Gmyl et al.,
1993]. Discovery of dependence of neurovirulence of picornaviruses on the
structure and functional efficiency of translational cis-elements of their
RNAs [Svitkin et al., 1985; Pilipenko et al., 1995; 1999]. Characterization
of protein trans-factors controlling translation of viral RNAs [Svitkin et
al., 1988; 1994; Pilipenko et al., 2000; 2001; Pestova et al., 2001]. First
cell-free translation of the tick-borne encephalitis (flavivirus) RNA and
demonstration that the proteins of this virus are generated by membrane-dependent
limited proteolysis of a high-molecular-mass precursor and mapping of the
genes for structural protein of this virus [Svitkin et al., 1978; 1981; 1984;
Lyapustin et al., 1986]. Discovery of differences in the molecular mechanisms
of translational shut-off induced by different picornaviruses [Svitkin et
al., 1978]. First biochemical evidence for the existence of intermolecular
recombination between RNA genomes [Romanova et al., 1980]. Elaboration of
models for replicative (template-switch) RNA recombination [Romanova et al.,
1986; Tolskaya et al., 1987; Pilipenko et al., 1995]. Discovery of nonreplicative
recombination between viral RNA genomes [Gmyl et al., 1999; 2003]. Introduction
of recombinational analysis for genetic mapping picornavirus functions, in
particular, attenuation determinants of poliovirus vaccine strains [Agol
et al., 1984]. Discovery of circular [Romanova, Agol, 1979] and palindromic
[Senkevich et al., 1980] forms of virus-specific RNAs. Discovery of participation
of host proteins in replication of picornavirus RNA [Dmitrieva et al., 1979].
Structural and functional characterization of a cis-element involved in the
initiation of negative strands of enterovirus RNA [Pilipenko et al., 1992;
1996]. Discovery of a kinetic coupling between substrate (rNTP) synthesis
and polymerization of picornavirus RNA [Koonin, Agol, 1982; 1984]. Discovery
of apoptosis-inducing and apoptosis-preventing functions of poliovirus [Tolskaya
et al., 1995]. Poliovirus-induced cell death may result from one of the competing
programs, apoptosis or canonical cytopathic effect [Agol et al., 1998; 2000].
The poliovirus-triggered apoptotic program involves mitochondrial damage
accompanied by the exit of pro-apoptotic factors, whereas one of the anti-apoptotic
mechanisms involves aberrant processing of caspase-9 [Belov et al., 2003]
but the implementation of this program may vary in a host-dependent way [Romanova
et al., 2005] . Poliovirus non-structural protein 3A reduces presentation
of TNF- receptor (and of some other receptors) on cellular membrane, suppressing
thereby the ability of TNF- to induce apoptosis of the infected cells [Neznanov
et al., 2001]. Poliovirus infection destroys, through the protease activity
of its protein 2A, nuclear pores and consequently the barrier function of
nuclear envelope, facilitating thereby bidirectional nucleo-cytoplasmic protein
trafficking [Belov et al., 1999, 2004]. Another picornavirus, encephalomyocarditis
virus, induces similar alterations in nucleo-cytoplasmic traffic but in this
case the effect is due to the viral leader protein devoid of any known enzymatic
activity [Lidsky et al., 2006].It is demonstrated that the majority of polioviruses
isolated from patients with vaccine-associated poliomyelitis are represented
by intertypic recombinants [Lipskaya et al., 1991]. Derivatives of the Sabin
poliovaccine exhibit a significant capacity to circulate in poorly immunized
[Korotkova et al., 2003; Cherkasova et al., 2005] and apparently adequately
immunized [Cherkasova et al., 2002; 2003] human populations. Oligonucleotide
microarray-based methods for characterization of genomes of poliovaccine
derivatives have been worked out [Cherkasova et al., 2003]. The genomes of
wild polioviruses circulating on the territory of the former USSR have been
characterized and the possible routes of their circulation were suggested
[Lipskaya et al., 1995]. Some general regularities of evolution of wild and
vaccine polioviruses have been revealed [Gavrilin et al., 2000; Agol, 2002,
2006].
Some important publications:
1. Svitkin YV, Agol VI. Complete translation of encephalomyocarditis virus
RNA and faithful cleavage of virus-specific proteins in a cell-free system
from krebs-2 cells. FEBS Lett. 1978; 87: 7-11.
2. Svitkin YV, Gorbalenya AE, Kazachkov YA. Agol VI. Encephalomyocarditis
virus-specific polypeptide p22 possessing a proteolytic activity. FEBS Lett.
1979; 108: 6-9.
3. Romanova LI, Tolskaya EA, Kolesnikova MS, Agol VI. Biochemical evidence
for intertypic genetic recombination of polioviruses. FEBS Lett. 1980; 118:
109-12.
4. Agol VI, Grachev VP, Drozdov SG, Frolova MP, Kolesnikova MS, Kozlov
VG, Ralph NM, Romanova LI, Tolskaya EA, Tyufanov AV, Viktorova EG. Construction
and pro-perties of intertypic poliovirus recombinants: First approximation
mapping of the major determinants of neurovirulence. Virology. 1984; 136:
41-55.
5. Svitkin YV, Maslova SV, Agol VI. The genomes of attenuated and virulent
poliovirus strains differ in their in vitro translation efficiencies. Virology.
1985; 147: 243-52.
6. Romanova LI, Blinov VM, Tolskaya EA, Viktorova EG, Kolesnikova MS,
Guseva E A, Agol VI. The pimary structure of crossover regions of intertypic
poliovirus recombinants: a model of recombination between RNA genomes. Virology.
1986; 155: 202-13.
7. Svitkin YV, Pestova TV, Maslova SV, Agol VI. Point mutations modify
the response of poliovirus RNA to a translation initiation factor: a comparison
of neurovirulent and attenuated strains. Virology. 1988; 166: 394-404.
8. Pilipenko EV, Blinov VM, Romanova LI, Sinyakov AN, Maslova SV, Agol
VI. Conserved structural domains in the 5'-untranslated region of picornaviral
genomes: an analysis of the segment controlling translation and neurovirulence.
Virology. 1989; 168: 201-9.
9. Pilipenko EV, Blinov VM, Chernov TM, Agol VI. Conservation of the secondary
structure elements of the 5'-untranslated region of cardio- and aphthovirus
RNAs. Nucl Acids Res. 1989; 17: 5701-11.
10. Lipskaya GYu, Muzychenko AR, Kutitova OK, Maslova SV, Equestre M,
Drozdov SG, Perez-Bercoff R, Agol VI. Frequent isolation of intertypic poliovirus
recombinants with serotype 2 specificity from vaccine-associated polio cases.
J Med Virol. 1991; 35: 290-6.
11. Pilipenko EV, Gmyl AP, Maslova SV, Svitkin YV, Sinyakov AN, Agol VI.
Prokaryotic-like cis element in the cap-independent internal initiation of
translation on picornavirus RNA. Cell. 1992; 68: 119-31.
12. Teterina NL, Kean KM, Gorbalenya AE, Agol VI, Girard M. Analysis of
functional significance of amino acid residues in the putative NTP-binding
pattern of the poliovirus 2C protein. J Gen Virol. 1992; 73: 1977-86.
13. Cho MW, Richards OC, Dmitrieva TM, Agol VI, Ehrenfeld E. RNA duplex
unwinding activity of poliovirus RNA-dependent RNA polymerase 3Dpol. J Virol.
1994; 67: 3010-8.
14. Tolskaya EA, Romanova LI, Kolesnikova MS, Gmyl AP, Gorbalenya AE,
Agol VI. Genetic studies on the NTP-binding pattern containing 2C protein
of poliovirus: Possible mechanism of guanidine effect on 2C function and
evidence for importance of 2C oligomerization. J Mol Biol. 1994; 236: 1310-23.
15. Pilipenko EV, Gmyl AP, Maslova SV, Belov GA, Sinyakov AN, Huang M,
Brown TDK, Agol VI. Starting window, distinct element in the cap-independent
internal initiation of translation on picornaviral RNA. J Mol Biol. 1994;
241: 398-414.
16. Tolskaya EA, Romanova LI, Kolesnikova MS, Ivannikova TA, Smirnova
EA, Raikhlin NT, Agol VI. Apoptosis-inducing and apoptosis-preventing functions
of poliovirus. J Virol. 1995; 69: 1181-9.
17. Pilipenko EV, Poperechny KV, Maslova SV, Melchers WJG, Bruins Slot
HJ, Agol VI. Cis-element, oriR, involved in the initiation of (-) strand
poliovirus RNA: a quasi-globular multi-domain RNA structure maintained by
tertiary ("kissing") interactions. EMBO J. 1996; 119: 5428-36.
18. Gmyl AP, Belousov EV, Maslova SV, Khitrina EV, Chetverin AB, Agol
VI. Nonreplicative RNA recombination in poliovirus. J Virol. 1999; 73: 8958-65.
19. Belov GA, Evstafieva AG, Mikitas OV, Vartapetian AB, Agol VI. Early
alteration of nucleo-cytoplasmic traffic induced by some RNA viruses. Virology.
2000; 275: 244-8.
20. Pilipenko EV, Pestova TV, Kolupaeva VG, Khitrina EV, Poperechnaya
AN, Agol VI, Hellen CUT. A cell-cycle dependent protein serves as a template-specific
translation initiation factor. Genes Dev. 2000; 14: 2028-45.
Some publications of 2001-2003:
1. Pestova TV, Kolupaeva VG, Lomakin IB, Pilipenko EV, Shatsky IN, Agol
VI, Hellen CU. Molecular mechanisms of translation initiation in eukaryotes.
Proc Natl Acad Sci USA. 2001; 98: 7029-36.
2. Neznanov N, Kondratova A, Chumakov KM, Angres B, Zhumabayeva B, Agol
VI, Gudkov AV. Poliovirus protein 3A inhibits TNF-induced apoptosis by eliminating
TNF receptor from the cell surface. J Virol. 2001; 75: 10409-20.
3. Pilipenko EV, Viktorova EG, Guest ST, Agol VI, Roos RP. Cell-specific
proteins regulate viral RNA translation and virus-induced disease. EMBO J.
2001; 20: 6899-908.
4. Cherkasova EA, Korotkova EA, Yakovenko ML,. Ivanova OE, Eremeeva TP,
Chumakov KM, Agol VI. Long-term circulation of vaccine-derived poliovirus
that causes paralytic disease. J Virol. 2002; 76: 6791-9.
5. Agol VI. Picornavirus genome: An overview. In: B. Semler, E. Wimmer,
Eds. Molecular Biology of Picornàviruses. ASM Press, Washington, DC, 2002;
127-48.
6. Agol VI. Picornavirus genetics: An overview. In: In: B. Semler, E.
Wimmer Eds Molecular Biology of Picornàviruses. ASM Press, Washington, DC,
2002; 269-84.
7. Belov GA, Romanova LI, Tolskaya EA, Kolesnikova MS, Lazebnik YA, Agol
VI. The major apoptotic pathway activated and suppressed by poliovirus. J
Virol. 2003; 77: 45-56.
8. Cherkasova EA, Laassri M, Chizhikov V, Korotkova EA, Dragunsky E, Agol
VI, Chumakov KM. Microarray analysis of evolution of RNA viruses: Evidence
of circulation of virulent highly divergent vaccine- derived polioviruses.
Proc Natl Acad Sci USA 2003; 100: 9398-403.
9. Gmyl AP, Korshenko SA, Belousov EV, Khitrina EV, Agol VI. Nonreplicative
homologous RNA recombination: Promiscuous joining of RNA pieces? RNA. 2003;
9: 1221-31.
10. Korotkova EA, Park R, Cherkasova, EA, Lipskaya GYu, Chumakov KM, Feldman
EV, Kew OM, Agol VI. Retrospective analysis of a local cessation of vaccination
against poliomyelitis: a possible scenario for the future. J Virol. 2003;
77: 12460-5.
Some publications since 2004:
1. Belov GA, Lidsky PV, Mikitas OV, Egger D, Lukyanov KA, Bienz K, Agol
VI. 2004. Bidirectional increase in permeability of nuclear envelope upon
poliovirus infection and accompanying alterations of nuclear pores . J. Virol.
78: 10166-10177.
2. Kew OM, Wright PF, Agol VI, Delpeyroux F, Shimizu H, Nathanson N, and
Pallansch MA. 2004. Circulating vaccine-derived polioviruses: current state
of knowledge. Bulletin of the WHO 82(1):16-23.
3. Cherkasova EA, Yakovenko ML, Rezapkin GV, Korotkova EA, Ivanova OE,
Eremeeva TP, Krasnoproshina LI, Romanenkova NI, Rozaeva NR, Sirota L, Agol
VI, Chumakov KM. 2005. Spread of vaccine-derived poliovirus from a paralytic
case in immunodeficient child: an insight into natural evolution of oral
polio vaccine. J. Virol. 79:1062-1070.
4. Romanova LI, Belov GA, Lidsky PV, Tolskaya EA, Kolesnikova MS, Evstafieva
AG, Vartapetian AB, Egger, D, Bienz, K, Agol VI. 2005. Variability in apoptotic
response to poliovirus infection. Virology 331:292-306.
5. Agol VI, Chumakov KM, Ehrefeld E, Wimmer E. 2005. Don, t drop current
vaccine until we have new ones. Nature 435, p. 881.
6. Ãìûëü ÀÏ, Àãîë ÂÈ. 2005. Ìíîãîîáðàçèå ìåõàíèçìîâ ÐÍÊ ðåêîìáèíàöèè.
Ìîë. Áèîë. ¹4, ñ. 618-632.
7. Lidsky PV, Hato S, Bardina MV, Aminev AG, Palmenberg AC, van Kuppeveld
FJM and Agol VI. 2006. Nucleo-cytoplasmic traffic disorder induced by cardioviruses.
J. Virol. 80:2705-2717.
8. Ëèäñêèé ÏÂ, Àãîë ÂÈ. 2006. Êàê ïîëèîâèðóñ èçìåíÿåò êëåòêó? Âîïð. âèðóñîë.
¹1 ñ.4-11.
9. Â. È. Àãîë. 2006. Âèðóñû. Áîëüøàÿ Ðîññèéñêàÿ Ýíöèêëîïåäèÿ (â ïå÷àòè)
10. Agol VI. 2006. Vaccine-derived polioviruses. Biologicals. (in press)
11. Agol VI.. Molecular mechanisms of poliovirus variation and evolution.
Curr. Top. Microbiol. Immunol. 299:211.
12. Yakovenko ML, Cherkasova EA, Rezapkin GV, Ivanov AP, Ivanova OE, Eremeeva
TP, and Agol VI. 2006. Antigenic evolution of vaccine-derived polioviruses:
Changes in individual epitopes and relative stability of the overall immunological
properties. J. Virol. 80:2641-2653.