Derivation ofHerpesvirus saimiri-Transformed CD8+T Cell Lines with Noncytotoxic Anti-HIV Activity

Mackewicz, Carl E.; Orque, Roland; Jung, Jae U.; Levy, Jay A.

doi:10.1006/clin.1996.4292

Cited by 17 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These fluids contain an unknown CD8 + T cell antiviral factor (i.e., CAF) that can show antiviral activity in acute HIV infection assays (section VII.B). It is noteworthy that the presence in these fluids of other cytokines (e.g., TNF-α) that enhance HIV replication ( 185 ) may counter the antiviral activity observed with CD8 + T cell culture fluids ( 186 , 187 ). This control of HIV infection by soluble secreted factors was reviewed more than a decade ago ( 15 ).…”

Section: (V) the Cd8 + T Cell Antiviral Factor (Caf)mentioning

confidence: 99%

The CD8⁺T Cell Noncytotoxic Antiviral Responses

Morvan

Teque

Locher³

et al. 2021

Microbiol Mol Biol Rev

Self Cite

View full text Add to dashboard Cite

SUMMARY The CD8+ T cell noncytotoxic antiviral response (CNAR) was discovered during studies of asymptomatic HIV-infected subjects more than 30 years ago. In contrast to CD8+ T cell cytotoxic lymphocyte (CTL) activity, CNAR suppresses HIV replication without target cell killing. This activity has characteristics of innate immunity: it acts on all retroviruses and thus is neither epitope specific nor HLA restricted. The HIV-associated CNAR does not affect other virus families. It is mediated, at least in part, by a CD8+ T cell antiviral factor (CAF) that blocks HIV transcription. A variety of assays used to measure CNAR/CAF and the effects on other retrovirus infections are described. Notably, CD8+ T cell noncytotoxic antiviral responses have now been observed with other virus families but are mediated by different cytokines. Characterizing the protein structure of CAF has been challenging despite many biologic, immunologic, and molecular studies. It represents a low-abundance protein that may be identified by future next-generation sequencing approaches. Since CNAR/CAF is a natural noncytotoxic activity, it could provide promising strategies for HIV/AIDS therapy, cure, and prevention.

show abstract

Section: (V) the Cd8 + T Cell Antiviral Factor (Caf)mentioning

confidence: 99%

The CD8⁺T Cell Noncytotoxic Antiviral Responses

Morvan

Teque

Locher³

et al. 2021

Microbiol Mol Biol Rev

Self Cite

View full text Add to dashboard Cite

show abstract

“…Particularly, the IFN-g secretion can be stimulated to very high levels (Bro« ker et al 1993;De Carli et al 1993;Weber et al 1993). In addition, many of these clones secrete large amounts of the CC-chemokines MIP-1a, MIP-1b (macrophage in£ammatory protein 1b) and 556 H. Fickenscher RANTES, which correlates with their Th1 phenotype (Mackewicz et al 1997;Saha et al 1998;Schrum et al 1996). Third, the most striking functional alteration induced by HVS in infected human Tcells is a hyperresponsiveness to CD2 ligation (Mittru« cker et al 1992).…”

Section: (D) Changed Cellular Features After T-cell Transformationmentioning

confidence: 99%

Herpesvirus saimiri

Fickenscher

Fleckenstein

2001

Phil. Trans. R. Soc. Lond. B

101

100

View full text Add to dashboard Cite

Herpesvirus saimiri (saimiriine herpesvirus 2) is the classical prototype of the gamma(2)-herpesviruses or rhadinoviruses, which also contains a human member, the Kaposi's sarcoma-associated herpesvirus. The T-lymphotropic Herpesvirus saimiri establishes specific replicative and persistent conditions in different primate host species. Virtually all squirrel monkeys (Saimiri sciureus) are persistently infected with this virus. In its natural host, the virus does not cause disease, whereas it induces fatal acute T-cell lymphoma in other monkey species after experimental infection. The virus can be isolated by cocultivation of permissive epithelial cells with peripheral blood cells from naturally infected squirrel monkeys and from susceptible New World monkeys during the virus-induced disease. Tumour-derived and in vitro-transformed T-cell lines from New World monkeys release virus particles. Herpesvirus ateles is a closely related virus of spider monkeys (Ateles spp.) and has similar pathogenic properties to Herpesvirus saimiri in other New World primate species. Similar to other rhadinoviruses, the genome of Herpesvirus saimiri harbours a series of virus genes with pronounced homology to cellular counterparts including a D-type cyclin, a G-protein-coupled receptor, an interleukin-17, a superantigen homologue, and several inhibitors of the complement cascade and of different apoptosis pathways. Preserved function has been demonstrated for most of the homologues of cellular proteins. These viral functions are mostly dispensable for the transforming and pathogenic capability of the virus. However, they are considered relevant for the apathogenic persistence of Herpesvirus saimiri in its natural host. A terminal region of the non-repetitive coding part of the virus genome is essential for pathogenicity and T-cell transformation. Based on the pathogenic phenotypes and the different alleles of this variable region, the virus strains have been assigned to three subgroups, termed A, B and C. In the highly oncogenic subgroup C strains, the two virus genes stpC and tip are transcribed from one bicistronic mRNA and are essential for transformation and leukaemia induction. stpC fulfils the typical criteria of an oncogene; its product interacts with Ras and tumour necrosis factor-associated factors and induces mitogen-activated protein kinase and nuclear factor kappa B activation. Tip interacts with the RNA transport factor Tap, with signal transduction and activation of transcription factors, and with the T-cellular tyrosine kinase Lck, which is activated by this interaction and phosphorylates Tip as a substrate. It is of particular interest that certain subgroup C virus strains such as C488 are capable of transforming human T lymphocytes to stable growth in culture. The transformed human T cells harbour multiple copies of the viral genome in the form of stable, non-integrated episomes. The cells express only a few virus genes and do not produce virus particles. The transformed cells maintain the antigen specificity and many ...

show abstract

“…H. saimiri ‐induced transformation was also used to immortalize T cells from patients with multiple primary immunodeficiencies in order to analyze the nature of signaling defects in the immunodeficient cells (Rodriguezgallego et al, 1996; Stephan et al, 1996; Broker et al, 1997; Gallego et al, 1997; Altare et al, 1998; Alvarez‐Zapata et al, 1998; Pacheco‐Castro et al, 1998; Zapata et al, 1999; Allende et al, 2000; Rivero‐Carmena et al, 2000; Henning et al, 2001; Meinl et al, 2001; Nakamura et al, 2001). Likewise, immortalized T‐cell clones obtained from HIV‐positive patients were used to investigate various aspects of AIDS pathogenesis, including roles of several cytokines (Mackewicz et al, 1997; Saha et al, 1997) and HIV‐suppressing soluble factors (Copeland et al, 1996; Lacey et al, 1998; Saha et al, 1999; Mosoian et al, 2000).…”

Section: Possible Utility Of H Saimiri and Its Transformation‐relatementioning

confidence: 99%

Cell transformation byHerpesvirus saimiri

Tsygankov

2004

Journal Cellular Physiology

View full text Add to dashboard Cite

Herpesvirus saimiri (Saimiriine herpesvirus-2), a g2-herpesvirus (rhadinovirus) of non-human primates, causes T-lymphoproliferative diseases in susceptible organisms and transforms human and non-human T lymphocytes to continuous growth in vitro in the absence of stimulation. T cells transformed by H. saimiri retain many characteristics of intact T lymphocytes, such as the sensitivity to interleukin-2 and the ability to recognize the corresponding antigens. As a result, H. saimiri is widely used in immunobiology for immortalization of various difficult-to-obtain and/or -to-maintain T cells in order to obtain useful experimental models. In particular, H. saimiri-transformed human T cells are highly susceptible to infection with HIV-1 and -2. This makes them a convenient tool for propagation of poorly replicating strains of HIV, including primary clinical isolates. Therefore, the mechanisms mediating transformation of T cells by H. saimiri are of considerable interest. A single transformation-associated protein, StpA or StpB, mediates cell transformation by H. saimiri strains of group A or B, respectively. Strains of group C, which exhibit the highest oncogenic potential, have two proteins involved in transformation-StpC and Tip. Both proteins have been shown to dramatically affect signal transduction pathways leading to the activation of crucial transcription factors. This review is focused on the biological effects and molecular mechanisms of action of proteins involved in H. saimiri-dependent transformation.

show abstract

Derivation ofHerpesvirus saimiri-Transformed CD8+T Cell Lines with Noncytotoxic Anti-HIV Activity

Cited by 17 publications

References 29 publications

The CD8⁺T Cell Noncytotoxic Antiviral Responses

The CD8⁺T Cell Noncytotoxic Antiviral Responses

Herpesvirus saimiri

Cell transformation byHerpesvirus saimiri

Contact Info

Product

Resources

About

Derivation ofHerpesvirus saimiri-Transformed CD8+T Cell Lines with Noncytotoxic Anti-HIV Activity

Cited by 17 publications

References 29 publications

The CD8+T Cell Noncytotoxic Antiviral Responses

The CD8+T Cell Noncytotoxic Antiviral Responses

Herpesvirus saimiri

Cell transformation byHerpesvirus saimiri

Contact Info

Product

Resources

About

The CD8⁺T Cell Noncytotoxic Antiviral Responses

The CD8⁺T Cell Noncytotoxic Antiviral Responses