Molecular organization of Junin virus S RNA: complete nucleotide sequence, relationship with other members of the Arenaviridae and unusual secondary structures
In this study, overlapping cDNA clones covering the entire S RNA molecule of Junin virus, an arenavirus that causes Argentine haemorrhagic fever, were generated. The complete sequence of this 3400 nucleotide RNA was determined using the dideoxynucleotide chain termination method. The nucleocapsid protein (N) and the glycoprotein precursor (GPC) genes were identified as two non-overlapping open reading frames of opposite polarity, encoding primary translation products of 564 and 481 amino acids, respectively. Intracellular processing of the latter yields the glycoproteins found in the viral envelope. Comparison of the Junin virus N protein with the homologous proteins of other arenaviruses indicated that amino acid sequences are conserved, the identity ranging from 46 to 76%. The N-terminal half of GPC exhibits an even higher degree of conservation (54 to 82%), whereas the C-terminal half is less conserved (21 to 50%). In all comparisons the highest level of amino acid sequence identity was seen when Junin virus and Tacaribe virus sequences were aligned. The nucleotide sequence at the 5′ end of Junin virus S RNA is not identical to that determined of the other sequenced arenaviruses. However, it is complementary to the 3′-terminal sequences and may form a very stable panhandle structure (ΔG -242.7 kJ/mol) involving the complete non-coding regions upstream from both the N and GPC genes. In addition, a distinct secondary structure was identified in the intergenic region, downstream from the coding sequences; Junin virus S RNA shows a potential secondary structure consisting of two hairpin loops (ΔG -163.2 and -239.3 kJ/mol) instead of the single hairpin loop that is usually found in other arenaviruses. The analysis of the arenavirus S RNA nucleotide sequences and their encoded products is discussed in relation to structure and function.
AuperinD. D.,
McCormickJ. B.1989; Nucleotide sequence of the Lassa virus (Josiah strain) S genome RNA and amino acid sequence comparison of the N and GPC proteins to other arenaviruses. Virology 168:421–425
AuperinD. D.,
CompansR. W.,
BishopD. H. L.1982; Nucleotide sequence conservation at the 3′ termini of the virion RNA species of New World and Old World arenaviruses. Virology 121:200–203
AuperinD. D.,
GalinskiM.,
BishopD. H. L.1984a; The sequences of the N protein gene and intergenic region of the S RNA of Pichinde arenavirus. Virology 134:208–219
AuperinD.,
RomanowskiV.,
BishopD. H. L.1984b; Genetic analyses of Pichinde and LCM arenaviruses; evidence for a unique organization for Pichinde S RNA. In Segmented Negative Strand Viruses, Arenaviruses, Bunyaviruses and Orthomyxoviruses pp 51–57 Edited by
CompansR. W.,
BishopD. H. L.
New York: Academic Press;
AuperinD.,
RomanowskiV.,
GalinskiM. S.,
BishopD. H. L.1984c; Sequencing studies of Pichinde arenavirus S RNA indicate a novel coding strategy, an ambisense viral S RNA. Journal of Virology 52:897–904
AuperinD. D.,
SassoD. R.,
McCormickJ. B.1986; Nucleotide sequence of the glycoprotein gene and intergenic region of the Lassa virus S genome RNA. Virology 154:155–167
BishopD. H. L.1988; The ambisense coding strategy of the S RNA of arenaviruses. In Modern Trends in Virology pp 99–108 Edited by
BauerH.,
KlonkH. -D.,
ScholtissekC.
Heidelberg: Springer-Verlag;
BishopD. H. L.,
GouldK. G.,
AkashiH.,
Clerx-van HaasterC. M.1982; The complete sequence and coding content of snowshoe hare bunyavirus small (S) viral RNA species. Nucleic Acids Research 10:3703–3713
BuchmeierM. J.,
OldstoneM. B. A.1978; Identity of the viral protein responsible for serologic cross reactivity among the Tacaribe complex arenaviruses. In Negative Strand Viruses and the Host Cell pp 91–97 Edited by
MahyB. W. J.,
BarryR. D.
Orlando: Academic Press;
BuchmeierM. J.,
LewickiH. A.,
TomoriO.,
OldstoneM. B. A.1981; Monoclonal antibodies to lymphocytic choriomeningitis and Pichinde viruses: generation, characterizaton and cross-reactivity with other arenaviruses. Virology 113:73–85
BuchmeierM. J.,
SouthernP. J.,
ParekhB. S.,
WooddellM. K.,
OldstoneM. B. A.1987; Site-specific antibodies define a cleavage site conserved among arenavirus GPC glycoproteins. Journal of Virology 61:982–985
ChirgwinJ. M.,
PrzybylaA. E.,
McdonaldR. J.,
RutterW. J.1979; Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299
CleggJ. C. S.,
OramJ. D.1985; Molecular cloning of Lassa-virus RNA: nucleotide sequence and expression of the nucleocapsid protein gene. Virology 144:363–372
De MitriM. I.,
Martinez SegoviaZ.1971; Phytohemagglutinin unresponsiveness in leukopenia induced by Junin virus in guinea pigs. Acta virologica 16:234–238
De MitriM. I.,
Martinez SegoviaZ.1980; Biological activities of Junin virus proteins. II. Complement-fixing polypeptides associated with the soluble antigen and purified particles. Inter-virology 14:84–90
EnriaD. A.,
FrancoS. G.,
AmbrosioA.,
VallejosD.,
LewisS.,
MaizteguiJ.1986; Current status of the treatment of Argentine hemorrhagic fever. Medical Microbiology and Immunology 175:173–176
Franze-FernandezM. T.,
ZetinaC.,
IapalucciS.,
LuceroM. A.,
BoissouC.,
LopezR.,
ReyO.,
DaheliM.,
CohenG.,
ZaleinM.1987; Molecular structure and early events in the replication of Tacaribe arenavirus S RNA. Virus Research 7:309–324
GhiringhelliP. D.,
Rivera PomarR. V.,
BaroN. I.,
RosasM. F.,
GrauO.,
RomanowskiV.1989; Nucleocapsid protein gene of Junin arenavirus (cDNA) sequence. Nucleic Acids Research 17:8001
GrauO.,
Franze-FernandezM. T.,
RomanowskiV.,
RusticiS. M.,
RosasM. F.1981; Junin virus structure. In The Replication of Negative Strand Viruses pp 11–14 Edited by
BishopD. H. L.,
CompansR. W.
Amsterdam: Elsevier/North-Holland;
GrunsteinM.,
HognessD. S.1975; Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proceedings of the National Academy of Sciences, U.S.A. 72:3961–3965
HsuM.,
ParvinJ. D.,
GuptaS.,
KrystalM.,
PaleseP.1987; Genomic RNAs of influenza viruses are held in a circular conformation in virions and in infected cells by a terminal pan handle. Proceedings of the National Academy of Sciences, U.S.A 84:8140–8144
IapalucciS.,
LopezN.,
ReyO.,
ZakinM. M.,
CohenG. N.,
Franze-FernandezM. T.1989b; The 5′ region of Tacaribe virus L RNA encodes a protein with a potential metal binding domain. Virology 173:357–361
JohnsonK. M.,
WebbP. A.,
JustinesG.1973; Biology of Tacaribe-complex viruses. In Lymphocytic Chroriomeningitis Virus and Other Arenaviruses pp 241–258 Edited by
Lehmann-GrubeF.
Berlin: Springer-Verlag;
MaizteguiJ. I.,
FernandezN. J.,
de DamilanoA. J.1979; Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome. Lancet ii:1216–1217
MaizteguiJ. I.,
FeuilladeM.,
BriggilerA.1986; Progressive extension of the endemic area and changing incidence of AHF. Medical Microbiology and Immunology 175:73–78
PalmerE. L.,
ObijeskiJ. F.,
WebbP. A.,
JohnsonK. M.1977; The circular segmented nucleocapsid of an arenavirus-Tacaribe virus. Journal of General Virology 36:541–545
PfauC. J.,
BergoldG. H.,
CasalsJ.,
JohnsonK. M.,
MurphyF. A.,
PedersenI. R.,
RawlsW. E.,
RoweW. P.,
WebbP. A.,
WeissenbacherM. C.1974; Arenaviruses. Intervirology 4:207–210
RomanowskiV.,
BishopD. H. L.1985; Conserved sequences and coding of two strains of lymphocytic choriomeningitis virus (WE and ARM) and Pichinde arenavirus. Virus Research 2:35–51
RomanowskiV.,
MatsuuraY.,
BishopD. H. L.1985; Complete sequence of the S RNA of lymphocytic choriomeningitis virus (WE strain) compared to that of Pichinde arenavirus. Virus Research 3:101–114
RoweW. P.,
MurphyF. A.,
BergoldG. H.,
CasalsJ.,
HotchinJ.,
JohnsonK. M.,
Lehmann-GrubeF.,
MimsC. A.,
TraubE.,
WebbP. A.1970; Arenaviruses: proposed name for a newly defined virus group. Journal of Virology 5:651–652
SabattiniM. S.,
Gonzalez de RiosL. E.,
DiazG.,
VegaV. R.1977; Infeccion natural y experimental de roedores con virus Junin. Medicina Buenos Aires 37: supplement 3149–161
SalvatoM.,
ShimomayeE. M.1989; The complete sequence of lymphocytic choriomeningitis virus reveals a unique RNA structure and a gene for a zinc finger protein. Virology 173:1–10
SalvatoM.,
ShimomayeE.,
OldstoneM. B. A.1989; The primary structure of the lymphocytic choriomeningitis virus L gene encodes a putative RNA polymerase. Virology 169:377–384
SangerF.,
NicklenS.,
CoulsonA. R.1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A 74:5463–5467
SchwartzR. M.,
DayhoffM. O.1979Atlas of Protein Sequence and Structure pp 353–358 Edited by
DayhoffM. O.
Washington, D.C.: National Biomedical Research Foundation;
TaylorW. R.1987; Protein structure prediction. In Nucleic Acid and Protein Sequence Analysis, A Practical Approach pp 285–322 Edited by
BishopM. J.,
RawlingsC. J.
Oxford & Washington D.C.: IRL Press;
TinocoI.,
BorerP. N.,
DenglerB.,
LevineM. D.,
UhlenbeckO. C.,
CrothersD. M.,
GrallaJ.1973; Improved estimation of secondary structure in ribonucleic acids. Nature New Biology 246:40–41
VezzaA. C.,
ClewleyJ. P.,
GardG. P.,
AbrahamN. Z.,
CompansR. W.,
BishopD. H. L.1978; Virion RNA species of the arenaviruses Pichinde, Tacaribe and Tamiami. Journal of Virology 26:485–497
WeissenbacherM. C.,
CotoC. E.,
CalelloM. A.,
RondinoneS. N.,
DamonteE. B.,
FrigerioM. J.1982; Cross-protection in nonhuman primates against Argentine hemorrhagic fever. Infection and Immunity 35:425–430
WilsonS. M.,
CleggJ. C. S.1991; Sequence analysis of the S RNA of the African arenavirus Mopeia: an unusual secondary structure feature in the intergenic region. Virology 180:543–552
Molecular organization of Junin virus S RNA: complete nucleotide sequence, relationship with other members of the Arenaviridae and unusual secondary structures