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Journal of Virology, June 2004, p. 5564-5575, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5564-5575.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes UL31 and UL34

Ashley E. Reynolds ,{dagger},{ddagger} Li Liang,{dagger} and Joel D. Baines*

Department of Microbiology and Immunology, Cornell University, Ithaca, New York 14853

Received 18 November 2003/ Accepted 27 February 2004

The herpes simplex virus type 1 (HSV-1) UL31 and UL34 proteins are dependent on each other for proper targeting to the nuclear membrane and are required for efficient envelopment of nucleocapsids at the inner nuclear membrane. In this work, we show that whereas the solubility of lamins A and C (lamin A/C) was not markedly increased, HSV induced conformational changes in the nuclear lamina of infected cells, as viewed after staining with three different lamin A/C-specific antibodies. In one case, reactivity with a monoclonal antibody that recognizes an epitope in the lamin tail domain was greatly reduced in HSV-infected cells. This apparent HSV-induced epitope masking required both UL31 and UL34, but these proteins were not sufficient to mask the epitope in uninfected cells, indicating that other HSV proteins are also required. In the second case, staining with a rabbit polyclonal antibody that primarily recognizes epitopes in the lamin A/C rod domain revealed that UL34 is required for HSV-induced decreased availability of epitopes for reaction with the antibody, whereas UL31 protein was dispensable for this effect. Still another polyclonal antibody indicated virtually no difference in lamin A/C staining in infected versus uninfected cells, indicating that the HSV-induced changes are more conformational than the result of lamin depletion at the nuclear rim. Further evidence supporting an interaction between the nuclear lamina and the UL31/UL34 protein complex includes the observations that (i) overexpression of the UL31 protein in uninfected cells was sufficient to relocalize lamin A/C from the nuclear rim into nucleoplasmic aggregates, (ii) overexpression of UL34 was sufficient to relocalize some lamin A/C into the cytoplasm, and (iii) both UL31 and UL34 could directly bind lamin A/C in vitro. These studies suggest that the UL31 and UL34 proteins modify the conformation of the nuclear lamina in infected cells, possibly by direct interaction with lamin A/C, and that other proteins are also likely involved. Given that the nuclear lamina potentially excludes nucleocapsids from envelopment sites at the inner nuclear membrane, the lamina alteration may reflect a role of the UL31/UL34 protein complex in perturbing the lamina to promote nucleocapsid egress from the nucleus. Alternatively, the data are compatible with a role of the lamina in targeting the UL31/UL34 protein complex to the nuclear membrane.

* Corresponding author. Mailing address: Dept. of Microbiology and Immunology, VMC C5 131, Cornell University, Ithaca, NY 14853. Phone: (607) 253-3385. Fax: (607) 253-3384. E-mail: jdb11{at}cornell.edu.

{dagger} A.E.R. and L.L. contributed equally to this work.

{ddagger} Present address: Deptartment of Molecular Biology, Princeton University, Princeton, NJ 08544.

Journal of Virology, June 2004, p. 5564-5575, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5564-5575.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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