1. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 319, Worcester, Massachusetts 01605, USA
2. †Present address: Centre for Research in Infectious Diseases, University College Dublin, Belfield, Dublin 4, Ireland

Correspondence to: Mario Stevenson¹ Correspondence and requests for materials should be addressed to M.S. (Email: mario.stevenson@umassmed.edu).

Abstract

Primate lentiviruses such as human immunodeficiency type 1 (HIV-1) have the capacity to infect non-dividing cells such as tissue macrophages¹. In the process, viral complementary DNA traverses the nuclear envelope to integrate within chromatin². Given the intimate association between chromatin and the nuclear envelope³, we examined whether HIV-1 appropriates nuclear envelope components during infection. Here we show that emerin, an integral inner-nuclear-envelope protein, is necessary for HIV-1 infection. Infection of primary macrophages lacking emerin was abortive in that viral cDNA localized to the nucleus but integration into chromatin was inefficient, and conversion of viral cDNA to non-functional episomal cDNA increased. HIV-1 cDNA associated with emerin in vivo, and the interaction of viral cDNA with chromatin was dependent on emerin. Barrier-to-autointegration factor (BAF), the LEM (LAP, emerin, MAN) binding partner of emerin, was required for the association of viral cDNA with emerin and for the ability of emerin to support virus infection. Therefore emerin, which bridges the interface between the inner nuclear envelope and chromatin, may be necessary for chromatin engagement by viral cDNA before integration.

1. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 319, Worcester, Massachusetts 01605, USA
2. †Present address: Centre for Research in Infectious Diseases, University College Dublin, Belfield, Dublin 4, Ireland

Correspondence to: Mario Stevenson¹ Correspondence and requests for materials should be addressed to M.S. (Email: mario.stevenson@umassmed.edu).

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