In these patients, there are competing risks of death. Wedge resection reduced death caused by respiratory failure but resulted in poorer long-term prognosis than lobectomy. For patients with poor predictors of survival, such as predicted percent vital capacity of 80% or less, surgical resection should be limited.

Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) persistently maintains a plasmid containing the KSHV latent origin of replication (oriP) as a closed circular episome in dividing cells. In this study, we investigated the involvement of chromosome binding activity of LANA1 in persistent episome maintenance. Deletion of the N-terminal 22 amino acids of LANA1 (⌬N-LANA) inhibited the interaction with mitotic chromosomes in a human cell line, and the mutant concomitantly lost activity for the long-term episome maintenance of a plasmid containing viral oriP in a human B-cell line. However, a chimera of ⌬N-LANA with histone H1, a cellular chromosome component protein, rescued the association with mitotic chromosomes as well as the long-term episome maintenance of the oriP-containing plasmid. Our results suggest that tethering of KSHV episomes to mitotic chromosomes by LANA1 is crucial in mediating the long-term maintenance of viral episomes in dividing cells.Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) is a gamma 2 herpesvirus and is associated with the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease (5,6,10,17,21,24). KSHV can establish long-term persistent infections in tumor cells and lymphoma-derived cell lines. In such cells, the double-stranded KSHV DNA genome can persist as multiple copies of closed circular episomes (5, 9), like the genome of its close relative, Epstein-Barr virus (EBV).Two viral components can mediate the long-term episome maintenance of KSHV in infected cells. One is latency-associated nuclear antigen 1 (LANA1), encoded by open reading frame 73, and the other is a cis-acting DNA sequence (latent origin of replication [oriP]) in the 5Ј end of the KSHV genome (terminal repeat [TR] sequence) (1, 2, 7). LANA1 persistently maintains a plasmid containing multiple TRs as an episome in a human B-cell line (1, 2).Previous studies showed that LANA1 was directly bound to the KSHV TR sequence (2,8,11). Furthermore, an imperfect 20-bp palindrome in the TR sequence exhibited binding activity for LANA1, and a plasmid containing three TRs was persistently maintained as an episome in a human cell line (2, 11). Domain map analysis revealed that the C-terminal region of LANA1 bound to this 20-bp palindrome in the TR sequence (11). Since this region contains the LANA1 dimerization domain (22), it seems likely that LANA1 binds to the TR sequence as a dimer, like EBNA1, the episome maintenance protein of EBV.About 40 to 80 copies of episomes are stably maintained in KSHV-infected lymphoma cells in vivo (1, 4). The constant KSHV copy number in dividing cells indicates that KSHV has an efficient system for segregating viral episomes into two daughter cells in every cell division. In the present study, we examined the involvement of the chromosome interaction activity of LANA1 in long-term episome maintenance. A 22-amino-acid deletion from the N terminus of LANA1 (⌬N-LANA) inhibit...

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