scholarly journals Molecular Polymorphism of Kaposi's Sarcoma–Associated Herpesvirus (Human Herpesvirus 8) Latent Nuclear Antigen: Evidence for a Large Repertoire of Viral Genotypes and Dual Infection with Different Viral Genotypes

1999 ◽  
Vol 180 (5) ◽  
pp. 1466-1476 ◽  
Author(s):  
Shou‐Jiang Gao ◽  
Yan‐Jin Zhang ◽  
Jian‐Hong Deng ◽  
Charles S. Rabkin ◽  
Ornella Flore ◽  
...  
2007 ◽  
Vol 79 (10) ◽  
pp. 1562-1568 ◽  
Author(s):  
Vanda Akico Ueda Fick de Souza ◽  
Ligia Camera Pierrotti ◽  
Laura Masami Sumita ◽  
Wilton Santos Freire ◽  
Aluisio Augusto Cotrim Segurado ◽  
...  

1999 ◽  
Vol 73 (6) ◽  
pp. 5149-5155 ◽  
Author(s):  
Paul Kellam ◽  
Dimitra Bourboulia ◽  
Nicolas Dupin ◽  
Chris Shotton ◽  
Cyril Fisher ◽  
...  

ABSTRACT Human herpesvirus 8 (HHV-8; also designated Kaposi’s sarcoma-associated herpesvirus) is the likely etiological agent of Kaposi’s sarcoma (KS). HHV-8 encodes a latent nuclear antigen (LNA) which is the product of the viral gene orf 73. LNA is recognized by most infected patient sera and is the basis of current immunofluorescence assays used in epidemiological studies of HHV-8 infection. Here we describe the characterization of four monoclonal antibodies raised to the C-terminal third of LNA–glutathioneS-transferase fusion proteins. These monoclonal antibodies recognized discrete linear epitopes within the C terminus and repetitive region of LNA, detected antigen in primary effusion lymphoma (PEL) cells, and precipitated a 220- to 230-kDa protein doublet corresponding to LNA from HHV-8-infected PEL cell lines. In situ immunocytochemistry of KS lesions with these antibodies show that LNA is extensively expressed in KS spindle cells.


2000 ◽  
Vol 74 (18) ◽  
pp. 8532-8540 ◽  
Author(s):  
David R. Schwam ◽  
Randy L. Luciano ◽  
Shahana S. Mahajan ◽  
LaiYee Wong ◽  
Angus C. Wilson

ABSTRACT Human herpesvirus 8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus) is the causative agent of Kaposi's sarcoma and certain B-cell lymphomas. In most infected cells, HHV-8 establishes a latent infection characterized by the expression of latency-associated nuclear antigen (LANA) encoded by open reading frame 73. Although unrelated by sequence, there are functional similarities between LANA and the EBNA-1 protein of Epstein-Barr virus. Both accumulate as subnuclear speckles and are required for maintenance of the viral episome. EBNA-1 also regulates viral gene expression and is required for cell immortalization, suggesting that LANA performs similar functions in the context of HHV-8 infection. Here we show that LANA forms stable dimers, or possibly higher-order multimers, and that this is mediated by a conserved region in the C terminus. By expressing a series of truncations, we show that both the N- and C-terminal regions localize to the nucleus, although only the C terminus accumulates as nuclear speckles characteristic of the intact protein. Lastly, we show that LANA can function as a potent transcriptional repressor when tethered to constitutively active promoters via a heterologous DNA-binding domain. Domains in both the N and C termini mediate repression. This suggests that one function of LANA is to suppress the expression of the viral lytic genes or cellular genes involved in the antiviral response.


2002 ◽  
Vol 83 (1) ◽  
pp. 179-188 ◽  
Author(s):  
Karin Mattsson ◽  
Csaba Kiss ◽  
Georgina M. Platt ◽  
Guy R. Simpson ◽  
Elena Kashuba ◽  
...  

LANA, the major latency-associated nuclear antigen of Kaposi’s sarcoma herpesvirus/human herpesvirus-8 (KSHV/HHV-8), binds RING3 protein, one of five human homologues of the fsh (female sterile homeotic) gene product of Drosophila. In KSHV/HHV-8-infected cells LANA and the viral episomes accumulate in heterochromatin-associated nuclear bodies. Here we show that in several KSHV/HHV-8-negative cell lines derived from carcinomas, sarcomas and lymphomas, RING3 was expressed at low levels, primarily localized to the euchromatin, and dissociated from the chromosomes during mitosis. In contrast, in KSHV/HHV-8-infected body cavity lymphoma cells the bulk of RING3 localizes to the LANA nuclear bodies and remains associated with the chromosomes during cell division. KSHV/HHV-8-infected body cavity lymphoma cells expressed RING3 at much higher levels than cells without the virus. Transfection of full-length LANA, but not the C terminus alone, greatly induced RING3 gene expression, and LANA and RING3 co-localized even in the transfected cells, in the absence of KSHV/HHV-8 viral DNA. High levels of LANA expression led to the disappearance of heterochromatin in both human and mouse cells. We suggest that LANA and RING3 may create a local euchromatic microenvironment around the viral episomes that are anchored to the heterochromatin.


2000 ◽  
Vol 16 (3) ◽  
pp. 247-251 ◽  
Author(s):  
Lı́gia Camera Pierrotti ◽  
Laura Masami Sumita ◽  
Wilton Santos Freire ◽  
Hélio Hehl Caiaffa Filho ◽  
Vanda Akico Ueda Fick de Souza

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