The Interaction between HIV-1 Gag and Human Lysyl-tRNA Synthetase during Viral Assembly

Human lysyl-tRNA synthetase (LysRS) is a tRNA-binding protein that is selectively packaged into HIV-1 along with its cognate tRNALys isoacceptors. Evidence exists that Gag alone is sufficient for the incorporation of LysRS into virions. Herein, using both in vitro and in vivo methods, we begin to map regions in Gag and LysRS that are required for this interaction. In vitro reactions between wild-type and truncated HIV-1 Gag and human LysRS were monitored using GST-tagged molecules and glutathione-agarose chromatography. Gag/LysRS interaction in vivo was detected in 293FT cells cotransfected with plasmids coding for wild-type or mutant HIV-1 Gag and LysRS, either by monitoring Gag·LysRS complexes immunoprecipitated from cell lysate with anti-LysRS or by measuring the ability of LysRS to be packaged into budded Gag viral-like particles. Based on these studies, we conclude that the Gag/LysRS interaction depends upon Gag sequences within the C-terminal domain of capsid (the last 54 amino acids) and amino acids 208–259 of LysRS. The latter domain includes the class II aminoacyl-tRNA synthetase consensus sequence known as motif 1. Both regions have been implicated in homodimerization of capsid and LysRS, respectively. Sequences falling outside these amino acid stretches can be deleted from either molecule without affecting the Gag/LysRS interaction, further supporting the observation that LysRS is incorporated into Gag viral-like particles independent of its ability to bind tRNALys. Human lysyl-tRNA synthetase (LysRS) is a tRNA-binding protein that is selectively packaged into HIV-1 along with its cognate tRNALys isoacceptors. Evidence exists that Gag alone is sufficient for the incorporation of LysRS into virions. Herein, using both in vitro and in vivo methods, we begin to map regions in Gag and LysRS that are required for this interaction. In vitro reactions between wild-type and truncated HIV-1 Gag and human LysRS were monitored using GST-tagged molecules and glutathione-agarose chromatography. Gag/LysRS interaction in vivo was detected in 293FT cells cotransfected with plasmids coding for wild-type or mutant HIV-1 Gag and LysRS, either by monitoring Gag·LysRS complexes immunoprecipitated from cell lysate with anti-LysRS or by measuring the ability of LysRS to be packaged into budded Gag viral-like particles. Based on these studies, we conclude that the Gag/LysRS interaction depends upon Gag sequences within the C-terminal domain of capsid (the last 54 amino acids) and amino acids 208–259 of LysRS. The latter domain includes the class II aminoacyl-tRNA synthetase consensus sequence known as motif 1. Both regions have been implicated in homodimerization of capsid and LysRS, respectively. Sequences falling outside these amino acid stretches can be deleted from either molecule without affecting the Gag/LysRS interaction, further supporting the observation that LysRS is incorporated into Gag viral-like particles independent of its ability to bind tRNALys. The life cycle of HIV-1 1The abbreviations used are: HIV-1, human immunodeficiency virus, type 1; LysRS, lysyl-tRNA synthetase; IleRS, isoleucine-tRNA synthetase; ProRS, proline-tRNA synthetase; GlnRS, glutamine-tRNA synthetase; ArgRS, arginine-tRNA synthetase; TrpRS, tryptophan-tRNA synthetase; MetRS, methionine-tRNA synthetase; TyrRS, tyrosine-tRNA synthetase; AsnRS, asparagine-tRNA synthetase; Gag, HIV-1 precursor protein containing sequences coding for HIV-1 structural proteins; Gag-Pol, HIV-1 precursor protein containing sequences coding for retroviral structural proteins and retroviral enzymes; VLP, viral-like-particle; Z, zipper; GST, glutathione S-transferase; TNE, Tris sodium chloride EDTA. has been intensely studied (for recent review see Ref. 1Swanstrom R. Wills J.W. Coffin J. Hughes S. Varmus H. Retroviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1997: 263-334Google Scholar). Upon infection of a cell by HIV-1, the viral RNA genome is copied into a double-stranded cDNA by the viral enzyme reverse transcriptase. tRNALys3 is required to initiate reverse transcription (2Mak J. Kleiman L. J. Virol. 1997; 71: 8087-8095Crossref PubMed Google Scholar). The resultant viral DNA is translocated into the nucleus of the infected cell where it integrates into the host cell DNA and codes for viral mRNA and proteins. Proteins comprising the viral structure include both the glycosylated envelope proteins (glycoproteins 120 and 41) and mature proteins resulting from the processing of the large precursor protein, Gag (Pr55gag): matrix (MAp11), capsid (CAp24), and nucleocapsid (NCp7). Gag also contains C-terminal sequences for the p6 protein, which is believed to play a role in viral budding from the cell. The three viral enzymes used in the HIV-1 life cycle result from the processing of another precursor Gag-Pol (Pr160gag-pol) and are protease (PRp11), reverse transcriptase (RTp66/p51), and integrase (INp32). Both Gag and Gag-Pol are translated from the same full-length viral RNA, and this RNA, which also serves as the viral genomic RNA, is packaged into assembling virions via binding to nucleocapsid sequences in Gag (3Berkowitz R. Fisher J. Goff S.P. Krausslich H.G. Morphogenesis and Maturation of Retroviruses.Vol. 214. Springer-Verlag New York Inc., New York1996: 177-218Google Scholar, 4Geigenmüller U. Linial M.L. J. Virol. 1996; 70: 667-671Crossref PubMed Google Scholar). The in vivo interaction of Gag with Gag-Pol has also been well documented (5Park J. Morrow C.D. J. Virol. 1992; 66: 6304-6313Crossref PubMed Google Scholar, 6Smith A.J. Cho M.I. Hammarskjöld M.L. Rekosh D. J. Virol. 1990; 64: 2743-2750Crossref PubMed Google Scholar, 7Smith A.J. Srivivasakumar N. Hammarskjöld M.-L. Rekosh D. J. Virol. 1993; 67: 2266-2275Crossref PubMed Google Scholar, 8Srinivasakumar N. Hammarskjöld M.-L. Rekosh D. J. Virol. 1995; 69: 6106-6114Crossref PubMed Google Scholar), and Gag-Pol is carried into the assembling Gag particle by its interaction with Gag protein, probably through intermolecular interactions between homologous Gag sequences. The Gag and Gag-Pol proteins assemble at the cell membrane, and during budding from the cell, the viral protease, PRp11, is activated and cleaves these two precursor precursors into the proteins found in the mature virion. The major tRNALys isoacceptors in mammalian cells, tRNALys1,2 and tRNALys3, are also selectively packaged into the virion during its assembly (9Jiang M. Mak J. Ladha A. Cohen E. Klein M. Rovinski B. Kleiman L. J. Virol. 1993; 67: 3246-3253Crossref PubMed Google Scholar). Gag protein is capable of forming extracellular Gag viral-like particles (VLPs), which are made by transfecting cells with a plasmid coding only for the Gag protein, but the additional presence of Gag-Pol is required for the packaging of tRNALys into either Gag VLPs or into HIV-1 (10Mak J. Jiang M. Wainberg M.A. Hammarskjold M.-L. Rekosh D. Kleiman L. J. Virol. 1994; 68: 2065-2072Crossref PubMed Google Scholar). Increasing the amount of tRNALys3 incorporated into HIV-1 results in a viral population with increased levels of tRNALys3 annealed to the viral RNA genome and increased infectivity (11Gabor J. Cen S. Javanbakht H. Niu M. Kleiman L. J. Virol. 2002; 76: 9096-9102Crossref PubMed Scopus (57) Google Scholar). In addition to the tRNALys isoacceptors, human lysyl-tRNA synthetase (LysRS), the enzyme that aminoacylates tRNALys, is also selectively packaged into HIV-1 during its assembly (12Cen S. Khorchid A. Javanbakht H. Gabor J. Stello T. Shiba K. Musier-Forsyth K. Kleiman L. J. Virol. 2001; 75: 5043-5048Crossref PubMed Scopus (116) Google Scholar, 13Cen S. Javanbakht H. Kim S. Shiba K. Craven R. Rein A. Ewalt K. Schimmel P. Musier-Forsyth K. Kleiman L. J. Virol. 2002; 76: 13111-13115Crossref PubMed Scopus (69) Google Scholar) and is a strong candidate for being the signal by which viral proteins recognize and selectively package the tRNALys isoacceptors. The packaging of LysRS into HIV-1 appears to be quite selective. Published work (12Cen S. Khorchid A. Javanbakht H. Gabor J. Stello T. Shiba K. Musier-Forsyth K. Kleiman L. J. Virol. 2001; 75: 5043-5048Crossref PubMed Scopus (116) Google Scholar, 13Cen S. Javanbakht H. Kim S. Shiba K. Craven R. Rein A. Ewalt K. Schimmel P. Musier-Forsyth K. Kleiman L. J. Virol. 2002; 76: 13111-13115Crossref PubMed Scopus (69) Google Scholar) indicates that human IleRS, ProRS, and TrpRS are not detected in the virion, whereas other work in one of our laboratories 2R. Halwani and L. Kleiman, unpublished work. indicates the additional absence of human ArgRS, GlnRS, MetRS, TyrRS, and AsnRS. In addition, Rous sarcoma virus, which uses tRNATrp as a primer tRNA for reverse transcription, contains TrpRS but not LysRS (13Cen S. Javanbakht H. Kim S. Shiba K. Craven R. Rein A. Ewalt K. Schimmel P. Musier-Forsyth K. Kleiman L. J. Virol. 2002; 76: 13111-13115Crossref PubMed Scopus (69) Google Scholar). An HIV-1 population contains, on average, ∼20–25 molecules of LysRS/virion (13Cen S. Javanbakht H. Kim S. Shiba K. Craven R. Rein A. Ewalt K. Schimmel P. Musier-Forsyth K. Kleiman L. J. Virol. 2002; 76: 13111-13115Crossref PubMed Scopus (69) Google Scholar) similar to the average number of tRNALys molecules/virion (14Huang Y. Mak J. Cao Q. Li Z. Wainberg M.A. Kleiman L. J. Virol. 1994; 68: 7676-7683Crossref PubMed Google Scholar). Our current hypothesis for the formation of a tRNALys-packaging complex includes a Gag·Gag-Pol complex interacting with a tRNALys·LysRS complex with Gag interacting with LysRS and Gag-Pol interacting with tRNALys. In addition to the reports cited above that provide evidence for an interaction between Gag and Gag-Pol, evidence supporting this model includes the following. 1) Whereas the incorporation of tRNALys into viruses requires Gag-Pol (10Mak J. Jiang M. Wainberg M.A. Hammarskjold M.-L. Rekosh D. Kleiman L. J. Virol. 1994; 68: 2065-2072Crossref PubMed Google Scholar), the incorporation of LysRS into HIV-1 occurs independently of tRNALys packaging, i.e. it is also packaged efficiently into Gag VLPs (12Cen S. Khorchid A. Javanbakht H. Gabor J. Stello T. Shiba K. Musier-Forsyth K. Kleiman L. J. Virol. 2001; 75: 5043-5048Crossref PubMed Scopus (116) Google Scholar), which do not selectively package tRNALys (10Mak J. Jiang M. Wainberg M.A. Hammarskjold M.-L. Rekosh D. Kleiman L. J. Virol. 1994; 68: 2065-2072Crossref PubMed Google Scholar). 2) Overexpression of LysRS in the cell results in a near doubling of the incorporation of both tRNALys and LysRS into HIV-1 (11Gabor J. Cen S. Javanbakht H. Niu M. Kleiman L. J. Virol. 2002; 76: 9096-9102Crossref PubMed Scopus (57) Google Scholar). 3) The ability of tRNALys to interact with LysRS is required for the incorporation of tRNALys into the virion (15Javanbakht H. Cen S. Musier-Forsyth K. Kleiman L. J. Biol. Chem. 2002; 277: 17389-17396Abstract Full Full PubMed Scopus Google Scholar). the interaction between Gag and LysRS be for the packaging of primer tRNALys3 into the virion and a for The of interaction between Gag and LysRS are in this using both in vitro and in vivo the amino acid sequences within the viral Gag precursor that mature viral proteins have been well the sequence and the large amount of structural and on aminoacyl-tRNA has the of the truncated LysRS used in these The of LysRS S. P. 1995; Full Full PubMed Scopus Google Scholar) and LysRS S. A. M. J. 1996; PubMed Scopus Google Scholar) have been LysRS is a class II forming a as with and M. J. D. 1990; PubMed Scopus Google Scholar, J. 1990; PubMed Scopus Google Scholar). The is a major for of the class human LysRS T. M. Musier-Forsyth K. PubMed Scopus Google Scholar, 1994; PubMed Scopus Google Scholar). is by an domain with a known as an which is of the found in of this domain not by human LysRS K. Stello T. H. T. Musier-Forsyth K. Schimmel P. J. Biol. Chem. 1997; Full Full PubMed Scopus Google Scholar), it has been that the truncated enzyme tRNA binding LysRS was to have for tRNALys the domain was M. M. P. M. J. Biol. Chem. 2002; 277: Full Full PubMed Scopus Google Scholar), and within the that in tRNA binding have been M. M. J. Biol. Chem. Full Full PubMed Scopus Google Scholar) domain was to provide LysRS with tRNA-binding of the class II are also by an and three consensus known as and M. J. D. 1990; PubMed Scopus Google Scholar). is of the II are or whereas and the The of these in LysRS is in in and were by D. Rekosh and M. L. Hammarskjold from of A.J. Cho M.I. Hammarskjöld M.L. Rekosh D. J. Virol. 1990; 64: 2743-2750Crossref PubMed Google Scholar). and were as M.A. B. H.G. J. Virol. PubMed Scopus Google Scholar). Gag for in 293FT cells were by of the cDNA and with and were in of the were into of The were used to these Gag reverse and reverse plasmids truncated Gag with in 293FT of the wild-type and mutant plasmids were using The cDNA was and with were in of the were into the of The were used to wild-type and mutant type reverse and plasmids wild-type and truncated Gag in E. contains cDNA full-length amino acids) human LysRS as K. Stello T. H. T. Musier-Forsyth K. Schimmel P. J. Biol. Chem. 1997; Full Full PubMed Scopus Google Scholar). wild-type and mutant LysRS, this cDNA was and with were in of the were into the of used the wild-type LysRS reverse and The resulting wild-type and mutant LysRS proteins into 293FT of the wild-type and mutant plasmids were using The cDNA was and with were in of the were into an of The were used to wild-type and mutant and reverse the same the reverse were used for C-terminal and The resulting wild-type and mutant proteins in E. of and HIV-1 cells are a of the human cell were with wild-type or mutant Gag and LysRS using to the was Gag VLPs were from by in a at for The was by in a at for through a The of was and in in a at for and proteins were with sodium of of of of The viral and cell were by by of protein by that are with HIV-1 capsid a for human LysRS and Laboratory, a for a for a to and a to C-terminal of HIV-1 which was used to of and of proteins was by using the from (for capsid and (for (for and human (for C-terminal and in and proteins were in E. The proteins were with at for were in and in and The were for on were at for The was used for of a of glutathione-agarose were as to the The from wild-type and mutant and were to of a of glutathione-agarose at for were with and with containing proteins were into with of Gag of and or of were to were at were three with and with of and for and was to for the protein, and of was used to of cells were from the and with 293FT cells from were in of was at for The was used for was to of and of protein were in of was to a of and the was for at The were with of and further in of for another at of protein as by the were with to protein for at The was three with and with the was of Tris and was and the was for to the proteins. the resulting was using of and LysRS with Gag in a of the domain of human LysRS. enzyme contains the three consensus sequences and 3) to of the class II as well as an to the domain K. Stello T. H. T. Musier-Forsyth K. Schimmel P. J. Biol. Chem. 1997; Full Full PubMed Scopus Google Scholar). LysRS and truncated LysRS were with on the and in E. The E. were to glutathione-agarose by three with containing and The were in binding containing HIV-1 The was three in containing and in containing were in and to were with either or to the wild-type and mutant LysRS and the amount of Gag to mutant LysRS where the Gag/LysRS for wild-type LysRS is a of The supporting these results are in and a of the with The a with whereas the other the wild-type and mutant of LysRS from the In a of the same was with that of the C-terminal amino acids from LysRS amino acids) not Gag binding but further of an additional C-terminal amino acids in that the sequence between amino acids and in motif of LysRS is required for binding to Gag in of and LysRS into Gag in truncated LysRS for to be packaged into Gag VLPs in 293FT cells were cotransfected with a plasmid coding for wild-type HIV-1 Gag and a plasmid coding for wild-type or or C-terminal deleted LysRS with The in the cell of the LysRS was and the results are in the in and B. of cell were with anti-LysRS and or both and LysRS, whereas only wild-type and mutant of LysRS. The of mutant are similar for of mutant LysRS but are the wild-type which was at 1. In the cell lysate of both and cells, is also protein with anti-LysRS that has a the LysRS The also appears in the viral lysate where its to the full-length LysRS has increased as (12Cen S. Khorchid A. Javanbakht H. Gabor J. Stello T. Shiba K. Musier-Forsyth K. Kleiman L. J. Virol. 2001; 75: 5043-5048Crossref PubMed Scopus (116) Google Scholar). The of this processing of full-length LysRS or from an is not The of wild-type LysRS from an plasmid in the two in which results in a LysRS the wild-type it contains a amino acid not to the of the LysRS in the The incorporation of the LysRS into virions is on the of and which of viral with anti-LysRS and of the amino acids not the ability of LysRS to be incorporated into Gag whereas the of the C-terminal amino acids LysRS The anti-LysRS used in the a amount of incorporated into the virus, whereas of this in the virion. The at the of the the the is to in the deleted LysRS the in and that a in LysRS for incorporation between amino acids and i.e. C-terminal not this do not in further that a for LysRS incorporation between amino acids and i.e. C-terminal of LysRS to and amino acid do not LysRS packaging, whereas LysRS with a C-terminal to and amino acid is not incorporated into Gag the results in and that the in vitro interaction between Gag and LysRS is the LysRS C-terminal includes the sequence between amino acids and whereas the packaging of LysRS into Gag VLPs is the C-terminal of LysRS includes amino acids The of results in vitro and in vivo indicates that the interaction between Gag and LysRS in vivo is to be a of and Gag with LysRS in and in and C-terminal Gag which were and in E. The E. were to glutathione-agarose as with wild-type K. Stello T. H. T. Musier-Forsyth K. Schimmel P. J. Biol. Chem. 1997; Full Full PubMed Scopus Google Scholar). LysRS, the were in and to were with either anti-LysRS or the amount of LysRS to mutant Gag for of the where the for wild-type Gag is a of The supporting these results are in and a of the with The a with alone the other the wild-type and mutant of Gag from the The of are a Gag is in (for see Ref. A. J. S.P. J. J. Virol. PubMed Google Scholar). conclude from these results that of the are a of the same with that of the amino acids of Gag not its interaction with LysRS, whereas the of an additional amino acids the interaction to of the wild-type binding of the amino acids C-terminal that the p6 and sequences not the Gag/LysRS interaction. these results that the C-terminal of the capsid in Gag is for the Gag/LysRS interaction. the ability of LysRS to be packaged into Gag VLPs of mutant Gag were with the plasmids coding for the Gag wild-type in which the sequence been with a domain to for in which both and p6 sequences were and was with a Gag that contains only the signal for in the matrix the C-terminal domain of the the sequence the and the p6 has been that of these can efficiently Gag VLPs M.A. B. H.G. J. Virol. PubMed Scopus Google Scholar). 293FT cells were with the plasmids coding for wild-type or mutant Gag and the ability of the Gag VLPs to package LysRS was by of with or anti-LysRS The in that of the the ability to package LysRS. The results that the C-terminal of capsid the domain be in binding LysRS, which is by the in vitro binding the in vitro interactions in that the Gag mutant which to LysRS, is not in binding LysRS. which domain of Gag was for interaction with LysRS in the of 293FT cells, the latter was with plasmids coding for wild-type Gag and of the mutant Gag The interaction was by with and the results are in the in the of the Gag in the using as a whereas the ability of anti-LysRS to the Gag type Gag, and interact with LysRS, but to these an interaction between amino acids and of capsid and LysRS and that the is not for which is with in vitro binding in both HIV-1 Gag and human LysRS have been used to map interacting both in vitro and in In wild-type and deleted of or were to glutathione-agarose and to bind to wild-type Gag or LysRS, was monitored and In 293FT cells were with plasmids coding for of either LysRS and or Gag and and the interaction between these proteins was monitored either by measuring the ability of LysRS to be incorporated into extracellular Gag VLPs or by using anti-LysRS the same sequences were to be for Gag/LysRS binding by of the of The of amino acids at the of capsid for interaction with LysRS in vitro was by the in in Gag to and amino acid and C-terminal in Gag to amino acid do not the in vitro interaction between Gag and wild-type LysRS. is by in vivo work that of of the matrix the of the amino acids in to the the of of and of sequences with the domain for the formation of Gag VLPs containing LysRS The in further to the for LysRS interaction to amino acids Based upon both the structure of the C-terminal of the HIV-1 capsid S. J. 1997; PubMed Scopus Google Scholar) and in vitro of in this A. J. S.P. J. J. Virol. PubMed Google Scholar, S. J. 1997; PubMed Scopus Google Scholar), the sequences in Gag that we have are for interaction with LysRS are of the capsid The of this in HIV-1 assembly is not this interaction is the which by interaction are probably the in Gag A. J. S.P. J. J. Virol. PubMed Google Scholar, S. J. 1997; PubMed Scopus Google Scholar). this which can homodimerization between capsid is also for interaction with LysRS, through the formation of a Our results also a role in Gag interaction for LysRS amino acid sequences within motif a domain known to be for of class II aminoacyl-tRNA S. P. 1995; Full Full PubMed Scopus Google Scholar, S. A. M. J. 1996; PubMed Scopus Google Scholar, J. B. M. D. 1993; PubMed Scopus Google Scholar, J. D. J. U. S. A. 1993; PubMed Scopus Google Scholar). In the of amino acids 208–259 in LysRS was by the that the of and the C-terminal of do not packaging of LysRS into Gag whereas with that include 208–259 packaging and LysRS was for its interaction with Gag in the that the LysRS mutant with Gag the LysRS mutant not 1) the from in vivo LysRS is a class synthetase with a of in in the of regions that are for binding to tRNALys, the and the domain this can interact with Gag The C-terminal of and sequences that the domain of LysRS. regions are also for Gag interaction sequence of from that the domain is in this enzyme K. Stello T. H. T. Musier-Forsyth K. Schimmel P. J. Biol. Chem. 1997; Full Full PubMed Scopus Google Scholar). our results that the interaction of LysRS with Gag occurs independent of its ability to bind to and tRNALys. that LysRS is packaged into Gag VLPs or mutant virions independent of tRNALys packaging (12Cen S. Khorchid A. Javanbakht H. Gabor J. Stello T. Shiba K. Musier-Forsyth K. Kleiman L. J. Virol. 2001; 75: 5043-5048Crossref PubMed Scopus (116) Google Scholar). we have that Gag VLPs efficiently package viral genomic RNA (10Mak J. Jiang M. Wainberg M.A. Hammarskjold M.-L. Rekosh D. Kleiman L. J. Virol. 1994; 68: 2065-2072Crossref PubMed Google Scholar) and LysRS (12Cen S. Khorchid A. Javanbakht H. Gabor J. Stello T. Shiba K. Musier-Forsyth K. Kleiman L. J. Virol. 2001; 75: 5043-5048Crossref PubMed Scopus (116) Google Scholar) but do not package tRNALys, which requires the additional presence of Gag-Pol (10Mak J. Jiang M. Wainberg M.A. Hammarskjold M.-L. Rekosh D. Kleiman L. J. Virol. 1994; 68: 2065-2072Crossref PubMed Google Scholar). Gag-Pol is required to the presence of tRNALys in the In to LysRS packaging, which can independent of tRNALys packaging, we that the latter was with LysRS interaction (15Javanbakht H. Cen S. Musier-Forsyth K. Kleiman L. J. Biol. Chem. 2002; 277: 17389-17396Abstract Full Full PubMed Scopus Google Scholar). In tRNA that were were also not efficiently tRNA packaging appears to upon interaction with LysRS, whereas LysRS packaging depends only on interaction with In our that for the homodimerization of capsid and LysRS are also for the interaction between these two observation that the interaction between LysRS and Gag formation using the same used by molecule for that LysRS be incorporated into the virion as a The of this interaction upon the of the Gag molecule be to regions of interactions between Gag molecules have been as at in the C-terminal of Gag and include the C-terminal of capsid S. J. 1997; PubMed Scopus Google Scholar, S. A. S. J. PubMed Scopus Google Scholar, S. PubMed Scopus Google Scholar, L. A. R. B. A. L. J. L. M. M. Biol. 1996; PubMed Scopus Google Scholar), the M.A. B. H.G. J. Virol. PubMed Scopus Google Scholar, M. J. H. J. Virol. 1995; 69: PubMed Google Scholar, Y. J. Virol. PubMed Scopus Google Scholar), nucleocapsid A. J. S.P. J. J. Virol. PubMed Google Scholar, S. J. Virol. 1995; 69: PubMed Google Scholar, 1996; Google Scholar, S. P. J. Virol. PubMed Google Scholar), and p6 L. L. Rovinski B. Cao Wills J.W. J. Virol. PubMed Google Scholar). the is of Gag molecules R. Wills J.W. Coffin J. Hughes S. Varmus H. Retroviruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1997: 263-334Google Scholar), and it is that only a of these molecules is in the interaction with LysRS. of LysRS and Gag be required in the interaction to sequences in these molecules to in this interaction. is probably the in vitro and in that sequences deleted both or of the in LysRS and in Gag are not required for the formation of the Gag·LysRS for in of the

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