Visualization of molecular biology: The LANA tether

Abstract

The latency-associated nuclear antigen (LANA) plays a central role in the biology and pathogenesis of Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV). Both classical and endemic KS in HIV-infected individuals and two lymphoproliferative diseases are associated with KSHV. During the latent phase of the viral life cycle in dividing tumor cells, the LANA protein ensures that viral genomes persist by supporting both the initiation of DNA replication and segregation of viral episomes (nonintegrated circular viral genomes) into daughter cells. Arguably, interrupting these complex LANA-dependent processes could be one of the most promising antiviral and antitumor therapeutic strategies. Hence, studying the molecular and cell biological details of LANA’s host/viral protein and chromatin interactions has been a focus in a number of laboratories since 1996. In PNAS, Grant et al. (1) propose an intriguing model of the architectural superstructure of LANA multimers bound to the terminal repeats (TRs) of KSHV genomes by applying superresolution microscopy in combination with computational modeling. Shortly after KSHV was discovered in KS lesions and primary effusion lymphoma (PEL) cells had been identified as a source for KS virus, reports described characteristic nuclear speckles that were observed by immunofluorescence when staining PEL cells with sera from patients who were PCR-positive for KSHV (2⇓–4). Soon after, cloning and sequencing of the complete KSHV genome and identification of the major KSHV latency-associated genes, in combination with transfection experiments, revealed that LANA encoded by ORF73 is the antigen that reacts with KSHV-positive patient antisera to give rise to “LANA speckles” (5, 6). To date, detection of LANA speckles is the gold standard for KSHV diagnostics (7). LANA is a large 220- … [↵][1]1To whom correspondence should be addressed. Email: rrenne{at}ufl.edu. [1]: #xref-corresp-1-1