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Journal of Virology, February 2004, p. 2006-2016, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.2006-2016.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Lv2, a Novel Postentry Restriction, Is Mediated by both Capsid and Envelope

Christian Schmitz,1 David Marchant,1 Stuart J. D. Neil,1 Keith Aubin,1 Sandra Reuter,2 Matthias T. Dittmar,2 and Áine McKnight1*

Wohl Virion Centre, Windeyer Institute of Medical Sciences, UCL, London W1T 4JF, United Kingdom,1 and Abteilung Virologie, Hygiene-Institut, D-69120 Heidelberg, Germany2

Received 26 June 2003/ Accepted 1 November 2003

The characterization of restrictions to lentivirus replication in cells identifies critical steps in the viral life cycle and potential therapeutic targets. We previously reported that a human immunodeficiency virus type 2 (HIV-2) isolate was restricted to infection in some human cells, which led us to identify a step in the life cycle of HIV-2 detected after reverse transcription but prior to nuclear entry. The block is bypassed with a vesicular stomatitis virus glycoprotein G (VSV-G) envelope (A. McKnight et al., J. Virol. 75:6914-6922, 2001). We hypothesized that, although the restriction is apparent at a post-reverse transcription step, the lack of progress results from a failure of the virus to reach a cellular compartment with access to the nucleus. Here we analyzed molecular clones of the restricted virus, MCR, and an unrestricted virus, MCN. Using sequence analysis and gene swapping, we mapped the viral determinants to gag and env. Site-directed mutagenesis identified a single amino acid at position 207 in CA to be responsible for the gag restriction. Pseudotype experiments indicate that this step is also important for the infection of cells by HIV-1. The HIV-1 NL4.3 core is restricted if supplied with a restricted MCR envelope but not with VSV-G. Also the NL4.3 envelope rescues the restricted core of HIV-2 MCR. Abrogation experiments with MLV demonstrate that the restriction is distinct from Fv1/Ref1/Lv1. We propose that this represents a new lentiviral restriction, Lv2. Thus, the envelope and capsid of HIV act to ensure that the virus is delivered into an appropriate cellular compartment that allows postentry events in viral replication to proceed efficiently.

* Corresponding author. Mailing address: Windeyer Institute of Medical Sciences, Wohl Virion Centre, 46 Cleveland St., London W1T 4JF, United Kingdom. Phone: 44 20 7679 9581. Fax: 44 20 7679 9555. E-mail: a.mcknight{at}ucl.ac.uk.

Journal of Virology, February 2004, p. 2006-2016, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.2006-2016.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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