8 documents found, page 1 of 1
Kaposi’s sarcoma herpesvirus latency-associated nuclear antigen broadly regulat...
Li, Shijun; Wang, Mengbo; Sciver, Nicholas Van; Szymula, Agnieszka; Tumuluri, Vinayak Sadasivam; George, Athira; Ramachandran, Akshaya; Raina, KomalKaposi’s sarcoma herpesvirus (KSHV) is a leading cause of malignancy in AIDS and current therapies are limited. Like all herpesviruses, KSHV infection can be latent or lytic. KSHV latency-associated nuclear antigen (LANA) is essential for viral genome persistence during latent infection. LANA also maintains latency by antagonizing expression and function of the KSHV lytic switch protein, RTA. Here, we find LANA...
Kaposi's sarcoma herpesvirus exploits the DNA damage response to circularize it...
Li, Shijun; Liu, Bing; Tan, Min; Juillard, Franceline; Szymula, Agnieszka; Álvarez, Ángel L.; Sciver, Nicholas Van; George, AthiraTo establish lifelong, latent infection, herpesviruses circularize their linear, double-stranded, DNA genomes through an unknown mechanism. Kaposi’s sarcoma (KS) herpesvirus (KSHV), a gamma herpesvirus, is tightly linked with KS, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV persists in latently infected cells as a multi-copy, extrachromosomal episome. Here, we show the KSHV genome rapid...
Macrophages drive KSHV B cell latency
Szymula, Agnieszka; Samayoa-Reyes, Gabriela; Ogolla, Sidney; Liu, Bing; Li, Shijun; George, Athira; Sciver, Nicholas Van; Rochford, RosemaryKaposi's sarcoma herpesvirus (KSHV) establishes lifelong infection and persists in latently infected B cells. Paradoxically, in vitro B cell infection is inefficient, and cells rapidly die, suggesting the absence of necessary factor(s). KSHV epidemiology unexpectedly mirrors that of malaria and certain helminthic infections, while other herpesviruses are ubiquitous. Elevated circulating monocytes are common in ...
MLL1 is regulated by KSHV LANA and is important for virus latency
Tan, Min; Li, Shijun; Juillard, Franceline; Chitas, Rute; Custódio, Tânia F.; Xue, Han; Szymula, Agnieszka; Sun, Qiming; Liu, Bing; Álvarez, Ángel L.Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat el...
KSHV LANA acetylation-selective acidic domain reader sequence mediates virus pe...
Juillard, Franceline; Miranda, Marta Pires de; Li, Shijun; Franco, Aura; Seixas, André F.; Liu, Bing; Álvarez, Ángel L.; Tan, Min; Szymula, AgnieszkaViruses modulate biochemical cellular pathways to permit infection. A recently described mechanism mediates selective protein interactions between acidic domain readers and unacetylated, lysine-rich regions, opposite of bromodomain function. Kaposi´s sarcoma (KS)-associated herpesvirus (KSHV) is tightly linked with KS, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV latently infects cells,...
Cross-species conservation of episome maintenance provides a basis for in vivo ...
Habison, Aline C.; Pires de Miranda, Marta; Beauchemin, Chantal; Tan, Min; A. Cerqueira, Sofia; Correia, Bruno; Ponnusamy, Rajesh; Usherwood, Edward J.Many pathogens, including Kaposi's sarcoma herpesvirus (KSHV), lack tractable small animal models. KSHV persists as a multi-copy, nuclear episome in latently infected cells. KSHV latency-associated nuclear antigen (kLANA) binds viral terminal repeat (kTR) DNA to mediate episome persistence. Model pathogen murine gammaherpesvirus 68 (MHV68) mLANA acts analogously on mTR DNA. kLANA and mLANA differ substantially ...
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat ...
Ponnusamy, Rajesh; Petoukhov, Maxim V.; Correia, Bruno; Custodio, Tania F.; Juillard, Franceline; Tan, Min; Pires de Miranda, Marta; Carrondo, Maria A.Latency-associated nuclear antigen (LANA) is central to episomal tethering, replication and transcriptional regulation of γ2-herpesviruses. LANA binds cooperatively to the terminal repeat (TR) region of the viral episome via adjacent LANA binding sites (LBS), but the molecular mechanism by which LANA assembles on the TR remains elusive. We show that KSHV LANA and MHV-68 LANA proteins bind LBS DNA using striking...
The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding d...
Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A.; McVey, Colin E.; Kaye, Kenneth M.Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA b...