The prototype foamy virus protease is active independently of the integrase domain

Retrovirology

Volumn 9, Issue , 2012, Pages

  Spannaus, Ralf ^a   Hartl, Maximilian J ^b   Wöhrl, Birgitta M ^b   Rethwilm, Axel ^a   Bodem, Jochen ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b UNIVERSITY OF BAYREUTH   (Germany)

Author keywords

Foamy virus; Gagpol fusion protein; Integrase; Parm; Regulation of protease activity

Indexed keywords

GAL POL FUSION PROTEIN; HYBRID PROTEIN; INTEGRASE; POL PROTEIN; PROTEINASE; RNA DIRECTED DNA POLYMERASE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME REGULATION; GENOME ANALYSIS; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PROTEIN CLEAVAGE; PROTEIN DETERMINATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROCESSING; SPUMA VIRUS; STRUCTURE ACTIVITY RELATION; VIRUS GENOME; VIRUS INFECTIVITY; VIRUS PARTICLE; WILD TYPE;

ASPARTIC ACID ENDOPEPTIDASES; ENZYME ACTIVATION; FUSION PROTEINS, GAG-POL; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, VIRAL; GENETIC COMPLEMENTATION TEST; HEK293 CELLS; HUMANS; INTEGRASES; PLASMIDS; PROTEIN STRUCTURE, TERTIARY; PROTEOLYSIS; RNA, VIRAL; RNA-DIRECTED DNA POLYMERASE; SIMIAN FOAMY VIRUS; TRANSFECTION; VIRAL PROTEINS;

HUMAN SPUMARETROVIRUS;

EID: 84860694307     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-9-41     Document Type: Article

References (27)

1. Enssle J, Jordan I, Mauer B, Rethwilm A. Foamy virus reverse transcriptase is expressed independently from the Gag protein. Proc Natl Acad Sci U S A 1996, 93:4137-4141. 10.1073/pnas.93.9.4137, 39500, 8633029.
2. Bodem J, Löchelt M, Winkler I, Flower RP, Delius H, Flügel RM. Characterization of the spliced pol transcript of feline foamy virus: the splice acceptor site of the pol transcript is located in gag of foamy viruses. J Virol 1996, 70:9024-9027. 191004, 8971036.
3. Yu SF, Baldwin DN, Gwynn SR, Yendapalli S, Linial ML. Human foamy virus replication: a pathway distinct from that of retroviruses and hepadnaviruses. Science 1996, 271:1579-1582. 10.1126/science.271.5255.1579, 8599113.
4. Löchelt M. Foamy virus transactivation and gene expression. Curr Top Microbiol Immunol 2003, 277:27-61. 10.1007/978-3-642-55701-9_2, 12908767.
5. Konvalinka J, Löchelt M, Zentgraf H, Flügel RM, Kräusslich HG. Active foamy virus proteinase is essential for virus infectivity but not for formation of a Pol polyprotein. J Virol 1995, 69:7264-7268. 189650, 7474150.
6. Löchelt M, Flügel RM. The human foamy virus pol gene is expressed as a Pro-Pol polyprotein and not as a Gag-Pol fusion protein. J Virol 1996, 70:1033-1040. 189909, 8551561.
7. Peters K, Wiktorowicz T, Heinkelein M, Rethwilm A. RNA and protein requirements for incorporation of the Pol protein into foamy virus particles. J Virol 2005, 79:7005-7013. 10.1128/JVI.79.11.7005-7013.2005, 1112116, 15890940.
8. Heinkelein M, Leurs C, Rammling M, Peters K, Hanenberg H, Rethwilm A. Pregenomic RNA is required for efficient incorporation of pol polyprotein into foamy virus capsids. J Virol 2002, 76:10069-10073. 10.1128/JVI.76.19.10069-10073.2002, 136505, 12208988.
9. Pfrepper KI, Rackwitz HR, Schnölzer M, Heid H, Löchelt M, Flügel RM. Molecular characterization of proteolytic processing of the Pol proteins of human foamy virus reveals novel features of the viral protease. J Virol 1998, 72:7648-7652. 110030, 9696869.
10. Enssle J, Fischer N, Moebes A, Mauer B, Smola U, Rethwilm A. Carboxy-terminal cleavage of the human foamy virus Gag precursor molecule is an essential step in the viral life cycle. J Virol 1997, 71:7312-7317. 192075, 9311808.
11. Hartl MJ, Bodem J, Jochheim F, Rethwilm A, Rösch P, Wöhrl BM. Regulation of Foamy Virus Protease Activity by Viral RNA - a Novel and Unique Mechanism Among Retroviruses. J Virol 2011, 85:4462-4469. 10.1128/JVI.02211-10, 3126251, 21325405.
12. Hartl MJ, Kretzschmar B, Frohn A, Nowrouzi A, Rethwilm A, Wöhrl BM. AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP. Nucleic Acids Res 2008, 36:1009-1016. 2241919, 18096624.
13. Lee EG, Roy J, Jackson D, Clark P, Boyer PL, Hughes SH, Linial ML. Foamy retrovirus integrase contains a Pol dimerization domain required for protease activation. J Virol 2010, 85:1655-1661. 3028899, 21123385.
14. Heinkelein M, Dressler M, Jarmy G, Rammling M, Imrich H, Thurow J, Lindemann D, Rethwilm A. Improved primate foamy virus vectors and packaging constructs. J Virol 2002, 76:3774-3783. 10.1128/JVI.76.8.3774-3783.2002, 136074, 11907217.
15. Imrich H, Heinkelein M, Herchenröder O, Rethwilm A. Primate foamy virus Pol proteins are imported into the nucleus. J Gen Virol 2000, 81:2941-2947.
16. Swiersy A, Wiek C, Reh J, Zentgraf H, Lindemann D. Orthoretroviral-like prototype foamy virus gag-pol expression is compatible with viral replication. Retrovirology 2011, 8:66. 10.1186/1742-4690-8-66, 3196705, 21843316.
17. Lindemann D, Rethwilm A. Foamy virus biology and its application for vector development. Viruses 2011, 3:561-585. 10.3390/v3050561, 3185757, 21994746.
18. Bodem J, Schied T, Gabriel R, Rammling M, Rethwilm A. Foamy virus nuclear RNA export is distinct from that of other retroviruses. J Virol 2011, 85:2333-2341. 10.1128/JVI.01518-10, 3067772, 21159877.
19. Baldwin DN, Linial ML. The roles of Pol and Env in the assembly pathway of human foamy virus. J Virol 1998, 72:3658-3665. 109586, 9557646.
20. Stange A, Mannigel I, Peters K, Heinkelein M, Stanke N, Cartellieri M, Göttlinger H, Rethwilm A, Zentgraf H, Lindemann D. Characterization of prototype foamy virus gag late assembly domain motifs and their role in particle egress and infectivity. J Virol 2005, 79:5466-5476. 10.1128/JVI.79.9.5466-5476.2005, 1082757, 15827161.
21. Peters K, Barg N, Gärtner K, Rethwilm A. Complex effects of foamy virus central purine-rich regions on viral replication. Virology 2008, 373:51-60. 10.1016/j.virol.2007.10.037, 18078974.
22. Heinkelein M, Schmidt M, Fischer N, Moebes A, Lindemann D, Enssle J, Rethwilm A. Characterization of a cis-acting sequence in the Pol region required to transfer human foamy virus vectors. J Virol 1998, 72:6307-6314. 109769, 9658069.
23. Hartl MJ, Wöhrl BM, Rösch P, Schweimer K. The solution structure of the simian foamy virus protease reveals a monomeric protein. J Mol Biol 2008, 381:141-149. 10.1016/j.jmb.2008.05.064, 18597783.
24. Hartl MJ, Schweimer K, Reger MH, Schwarzinger S, Bodem J, Rösch P, Wöhrl BM. Formation of transient dimers by a retroviral protease. Biochem J 2010, 427:197-203. 10.1042/BJ20091451, 20136635.
25. Hartl MJ, Mayr F, Rethwilm A, Wöhrl BM. Biophysical and enzymatic properties of the simian and prototype foamy virus reverse transcriptases. Retrovirology 2010, 7:5. 10.1186/1742-4690-7-5, 2835651, 20113504.
26. Stirnnagel K, Lüftenegger D, Stange A, Swiersy A, Müllers E, Reh J, Stanke N, Grosse A, Chiantia S, Keller H, et al. Analysis of prototype foamy virus particle-host cell interaction with autofluorescent retroviral particles. Retrovirology 2010, 7:45. 10.1186/1742-4690-7-45, 2887381, 20478027.
27. Müllers E, Uhlig T, Stirnnagel K, Fiebig U, Zentgraf H, Lindemann D. Novel functions of prototype foamy virus Gag glycine- arginine-rich boxes in reverse transcription and particle morphogenesis. J Virol 2011, 85:1452-1463. 10.1128/JVI.01731-10, 3028916, 21106749.