Analysis of the interactions of low-risk human papillomavirus type 11 (HPV11) L2 with karyopherin ␤ (Kap ␤) nuclear import receptors revealed that L2 interacted with Kap ␤ 1 , Kap ␤ 2 , and Kap ␤ 3 and formed a complex with the Kap ␣ 2 ␤ 1 heterodimer. HPV11 L2 contains two nuclear localization signals (NLSs)-in the N terminus and the C terminus-that could mediate its nuclear import via a classical pathway. Each NLS was functional in vivo, and deletion of both of them abolished L2 nuclear localization. Both NLSs interacted with the viral DNA. Thus, HPV11 L2 can interact with several karyopherins and the viral DNA and may enter the nucleus via multiple pathways.Human papillomavirus (HPV) virions consist of a single molecule of 8-kb double-stranded circular DNA contained within a spherical capsid composed of 72 L1 capsomers and the L2 minor capsid protein, estimated to have 36 molecules per capsid (10, 15). Although L1 expressed alone in mammalian cells harboring episomal DNA forms virions (18), L2 expression is required for efficient encapsidation of the viral DNA (15, 17). Expression and nuclear import of L2 during the productive stage precede the expression and nuclear translocation of L1 (5). Studies with HPV virions in raft cultures have shown that L2 participates in at least two steps in the production of infectious virus (7). L2 binds to cells (9,19) and interacts with ␤-actin and tSNARE syntaxin 18 (1, 20) and also facilitates the escape of the viral genome from the endocytic compartment after viral uncoating (8). Cleavage of L2 at a furin consensus site located in the N terminus was reported to be required for infection (14). Bovine papillomavirus type 1 (BPV1) L2 termini required for infectivity can function as nuclear localization signals (NLSs) mediating nuclear import via a classical pathway, and the C-terminal NLS (cNLS) can also interact with the viral DNA (4). These results, together with the colocalization of the incoming L2 and genome in the nucleus at ND10 (3), suggest that BPV1 L2 may facilitate the nuclear localization of the genome in the initial stages of infection. In a related virus, simian virus 40, nuclear import of simian virus 40 DNA is mediated by the VP3 capsid protein via interaction with the importin heterodimer (12).Active nuclear import of proteins is mediated by import receptors of the karyopherin ␤ (Kap ␤)/importin ␤ superfamily that interact with nucleoporins at the nuclear pore complex to transport the proteins into the nucleus. Binding of nuclear RanGTP to the Kap ␤s causes dissociation of the import complexes, leading to the release of the transported cargoes inside the nucleus (6, 11). In this study we investigated the interactions of the L2 minor capsid protein of low-risk HPV11 with import receptors and viral DNA and mapped its NLSs and DNA binding sites. The His-tagged HPV11 L2 contained in the pProEX HTb plasmid vector (16) was expressed in Escherichia coli BL21-CodonPlus and purified as previously described (2). We analyzed the interactions between His-tagged HPV11 L2...

DAB486IL-2 is an interleukin-2 receptor-specific cytotoxin which selectively targets and kills cells which bear the high-affinity form of the IL-2 receptor. Since elimination of activated T lymphocytes may be useful in the treatment of rheumatoid arthritis, the effect of DAB486IL-2 treatment in an animal model of arthritis was investigated. We demonstrated that rats treated with DAB486IL-2 during the induction phase of disease have delayed onset of symptoms and significantly reduced severity of inflammation as well as a depressed proliferative response to mycobacterial stimulation in vitro. In addition, the presence of preexisting antibodies to the molecule had no impact on the anti-arthritic effects observed in this model. These data suggest that DAB486IL-2 may have therapeutic potential in the treatment of rheumatoid arthritis.

To investigate the mechanisms of HIV-1 cytopathogenicity, functional biological HIV-1 clones were isolated from two infected children with high viral loads in vivo. Clone HC4 was isolated from a symptomatic child and clone GC6 8-4 was isolated from an asymptomatic child. These

Primate lentiviruses are thought to use the chemokine receptor CCR5 as the major coreceptor for entry into cells. Here we show that some variants of simian immunodeficiency virus (SIV) replicate efficiently in peripheral blood mononuclear cells (PBMCs) lacking a functional CCR5. There were differences in the replication patterns of sequential variants that evolved during SIVMne infection; the late-stage pathogenic variants were unable to replicate in PBMCs lacking CCR5, whereas the early-and intermediate-stage viruses replicated as well in PBMCs lacking CCR5 as they did in cells with wild-type CCR5. The coreceptor specificities of these sequential variants were compared using indicator cell lines expressing known SIV coreceptors. Among the known SIV coreceptors, there were none that were functional for the early and intermediate variants but not the late-stage variants, suggesting that the coreceptor used for replication in PBMCs may be a coreceptor that has not yet been described. Because some variants replicate with high efficiency in peripheral blood cells using this as yet uncharacterized cellular receptor, this coreceptor may be important for viral entry of some target cell populations in the host.

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