scholarly journals Interference with the Autophagic Process as a Viral Strategy to Escape from the Immune Control: Lesson from Gamma Herpesviruses

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Roberta Santarelli ◽  
Marisa Granato ◽  
Alberto Faggioni ◽  
Mara Cirone
Keyword(s):  
Immune Response ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Immune Control ◽  
Antiviral Immune Response ◽  
Human Cancers ◽  
Autophagic Process ◽  
Epstein Barr ◽  
Kaposi’S Sarcoma Associated Herpesvirus

We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi’s sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong toγ-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis.

scholarly journals Role of Kaposi's Sarcoma-Associated Herpesvirus C-Terminal LANA Chromosome Binding in Episome Persistence

2009 ◽  
Vol 83 (9) ◽  
pp. 4326-4337 ◽  
Author(s):  
Brenna Kelley-Clarke ◽  
Erika De Leon-Vazquez ◽  
Katherine Slain ◽  
Andrew J. Barbera ◽  
Kenneth M. Kaye
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Chromosome Association ◽  
Mitotic Chromosomes ◽  
Dividing Cells ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Self Association ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
Chromosome Binding

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) LANA is an 1,162-amino-acid protein that tethers terminal repeat (TR) DNA to mitotic chromosomes to mediate episome persistence in dividing cells. C-terminal LANA self-associates to bind TR DNA. LANA contains independent N- and C-terminal chromosome binding regions. N-terminal LANA binds histones H2A/H2B to attach to chromosomes, and this binding is essential for episome persistence. We now investigate the role of C-terminal chromosome binding in LANA function. Alanine substitutions for LANA residues 1068LKK1070 and 1125SHP1127 severely impaired chromosome binding but did not reduce the other C-terminal LANA functions of self-association or DNA binding. The 1068LKK1070 and 1125SHP1127 substitutions did not reduce LANA's inhibition of RB1-induced growth arrest, transactivation of the CDK2 promoter, or C-terminal LANA's inhibition of p53 activation of the BAX promoter. When N-terminal LANA was wild type, the 1068LKK1070 and 1125SHP1127 substitutions also did not reduce LANA chromosome association or episome persistence. However, when N-terminal LANA binding to chromosomes was modestly diminished, the substitutions in 1068LKK1070 and 1125SHP1127 dramatically reduced both LANA chromosome association and episome persistence. These data suggest a model in which N- and C-terminal LANA cooperatively associates with chromosomes to mediate full-length LANA chromosome binding and viral persistence.

scholarly journals Epstein-Barr Virus Latent Gene Expression in Primary Effusion Lymphomas Containing Kaposi's Sarcoma–Associated Herpesvirus/Human Herpesvirus-8

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1186-1191 ◽  
Author(s):  
Marcelo G. Horenstein ◽  
Roland G. Nador ◽  
Amy Chadburn ◽  
Elizabeth M. Hyjek ◽  
Giorgio Inghirami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Kaposi's Sarcoma ◽  
Epstein Barr Virus ◽  
Kaposi’S Sarcoma ◽  
Barr Virus ◽  
Low Levels ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Epstein Barr ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Primary effusion (body cavity–based) lymphoma (PEL) is a recently recognized subtype of malignant lymphoma that exhibits distinctive clinical and biological features, most notably its usual infection with the Kaposi's sarcoma–associated herpesvirus (KSHV). The vast majority of cases also contain Epstein-Barr virus (EBV). This dual viral infection is the first example of a consistent dual herpesviral infection in a human neoplasm and provides a unique model to study viral interactions. We analyzed the pattern of EBV latent gene expression to determine the pathogenic role of this agent in PELs. We examined five PELs coinfected with EBV and KSHV by reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. EBER1 mRNA, a consistent marker of viral latency, was positive in all PEL cases, although at lower levels than in the non-PEL controls due to EBER1 expression by only a variable subset of lymphoma cells. Qp-initiated mRNA, encoding only EBNA1 and characteristic of latencies I and II, was positive in all PEL cases. Wp- and Cp-initiated mRNAs, encoding all EBNAs and characteristic of latency III, were negative in all cases. LMP1 mRNA, expressed in latencies II and III, was present in three cases of PEL, although at very low levels that were not detectable at the protein level by immunohistochemistry. Low levels of LMP2A mRNA were detected in all cases. BZLF1, an early-intermediate lytic phase marker, was weakly positive in four cases, suggesting a productive viral infection in a very small proportion of cells, which was confirmed by ZEBRA antigen expression. Therefore, PELs exhibit a restricted latency pattern, with expression of EBNA1 in all cases, and low LMP1 and LMP2A levels.

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing

2007 ◽  
Vol 81 (15) ◽  
pp. 8225-8235 ◽  
Author(s):  
Hyun Jin Kwun ◽  
Suzane Ramos da Silva ◽  
Ishita M. Shah ◽  
Neil Blake ◽  
Patrick S. Moore ◽  
...  
Keyword(s):  
Antigen Processing ◽  
Kaposi's Sarcoma ◽  
Epstein Barr Virus ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Epstein Barr ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5′ or 3′ end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses.

scholarly journals Lytic and Latent Antigens of the Human Gammaherpesviruses Kaposi's Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Induce T-Cell Responses with Similar Functional Properties and Memory Phenotypes

2007 ◽  
Vol 81 (9) ◽  
pp. 4904-4908 ◽  
Author(s):  
Florian Bihl ◽  
Murli Narayan ◽  
John V. Chisholm ◽  
Leah M. Henry ◽  
Todd J. Suscovich ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Immunity ◽  
Kaposi's Sarcoma ◽  
Epstein Barr Virus ◽  
T Cell Responses ◽  
Kaposi’S Sarcoma ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT The cellular immunity against Kaposi's sarcoma-associated herpesvirus (KSHV) is poorly characterized and has not been compared to T-cell responses against other human herpesviruses. Here, novel and dominant targets of KSHV-specific cellular immunity are identified and compared to T cells specific for lytic and latent antigens in a second human gammaherpesvirus, Epstein-Barr virus. The data identify a novel HLA-B57- and HLA-B58-restricted epitope in the Orf57 protein and show consistently close parallels in immune phenotypes and functional response patterns between cells targeting lytic or latent KSHV- and EBV-encoded antigens, suggesting common mechanisms in the induction of these responses.

scholarly journals Role of Host MicroRNAs in Kaposi’s Sarcoma-Associated Herpesvirus Pathogenesis

Viruses ◽  
2014 ◽  
Vol 6 (11) ◽  
pp. 4571-4580 ◽  
Author(s):  
Zhiqiang Qin ◽  
Francesca Peruzzi ◽  
Krzysztof Reiss ◽  
Lu Dai
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

scholarly journals Epstein-Barr Virus Latent Gene Expression in Primary Effusion Lymphomas Containing Kaposi's Sarcoma–Associated Herpesvirus/Human Herpesvirus-8

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1186-1191 ◽  
Author(s):  
Marcelo G. Horenstein ◽  
Roland G. Nador ◽  
Amy Chadburn ◽  
Elizabeth M. Hyjek ◽  
Giorgio Inghirami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Kaposi's Sarcoma ◽  
Epstein Barr Virus ◽  
Kaposi’S Sarcoma ◽  
Barr Virus ◽  
Low Levels ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Epstein Barr ◽  
Kaposi’S Sarcoma Associated Herpesvirus

Abstract Primary effusion (body cavity–based) lymphoma (PEL) is a recently recognized subtype of malignant lymphoma that exhibits distinctive clinical and biological features, most notably its usual infection with the Kaposi's sarcoma–associated herpesvirus (KSHV). The vast majority of cases also contain Epstein-Barr virus (EBV). This dual viral infection is the first example of a consistent dual herpesviral infection in a human neoplasm and provides a unique model to study viral interactions. We analyzed the pattern of EBV latent gene expression to determine the pathogenic role of this agent in PELs. We examined five PELs coinfected with EBV and KSHV by reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. EBER1 mRNA, a consistent marker of viral latency, was positive in all PEL cases, although at lower levels than in the non-PEL controls due to EBER1 expression by only a variable subset of lymphoma cells. Qp-initiated mRNA, encoding only EBNA1 and characteristic of latencies I and II, was positive in all PEL cases. Wp- and Cp-initiated mRNAs, encoding all EBNAs and characteristic of latency III, were negative in all cases. LMP1 mRNA, expressed in latencies II and III, was present in three cases of PEL, although at very low levels that were not detectable at the protein level by immunohistochemistry. Low levels of LMP2A mRNA were detected in all cases. BZLF1, an early-intermediate lytic phase marker, was weakly positive in four cases, suggesting a productive viral infection in a very small proportion of cells, which was confirmed by ZEBRA antigen expression. Therefore, PELs exhibit a restricted latency pattern, with expression of EBNA1 in all cases, and low LMP1 and LMP2A levels.

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