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Journal of Virology, April 2007, p. 3317-3326, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.01866-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Correct Capsid Assembly Mediated by a Conserved YXXLGL Motif in Prototype Foamy Virus Gag Is Essential for Infectivity and Reverse Transcription of the Viral Genome{triangledown}

Ingrid Mannigel ,1,{dagger},{ddagger} Annett Stange,1,{dagger} Hanswalter Zentgraf,2 and Dirk Lindemann1*

Institut für Virologie, Medizinische Fakultät "Carl Gustav Carus," Technische Universität Dresden, Dresden,1 Deutsches Krebsforschungszentrum, Heidelberg, Germany2

Received 28 August 2006/ Accepted 5 January 2007

Unlike other retrovirus Gag proteins, the prototype foamy virus (PFV) p71gag protein is not processed into mature matrix (MA), capsid (CA), and nucleocapsid (NC) subunits. Little information about sequence motifs involved in FV capsid assembly and release is available. The recent analysis of candidate L-domain motifs in PFV Gag identified an evolutionarily conserved YXXL sequence motif with a potential function in capsid assembly. Here we provide support for the hypothesis that this motif does not function like a conventional L domain, by demonstrating that, unlike the PFV Gag PSAP L-domain motif, it cannot be functionally replaced by heterologous L-domain sequences. Furthermore, mutation of individual amino acids Y464, I466, L467, and L469, but not E465, to alanine led to reduced particle release and production of noninfectious, aberrant capsid structures, although relative structural protein incorporation and processing were not affected. In contrast, mutation of G468 to alanine resulted in an intermediate, temperature-sensitive phenotype characterized by reduced particle release and reduced infectivity. Despite similar relative RNA genome incorporation for all mutants, analysis and quantification of particle-associated viral nucleic acids demonstrated defects in genomic reverse transcription for all the noninfectious mutants, a process that, unlike that of orthoretroviruses, in the case of FVs takes place in the virus-producing cell. In correlation with the reduced infectivity, the G468A mutant displayed an intermediate level of genomic reverse transcription. Taken together, these results demonstrate that the conserved YXXLGL motif in PFV Gag is involved in correct capsid assembly, which in turn is essential for reverse transcription of the FV genome.

* Corresponding author. Mailing address: Institut für Virologie, Medizinische Fakultät "Carl Gustav Carus," Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany. Phone: 49-351-458-6210. Fax: 49-351-458-6314. E-mail: dirk.lindemann{at}mailbox.tu-dresden.de.

{triangledown} Published ahead of print on 17 January 2007.

{dagger} I.M. and A. S. contributed equally to this work.

{ddagger} Present address: Institut für Physiologie, Ludwig-Maximilians-Universität München, München, Germany.

Journal of Virology, April 2007, p. 3317-3326, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.01866-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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