HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structure

Zack, Jerome A.; Arrigo, Salvatore J.; Weitsman, Stacy; Go, Alan S.; Haislip, Allyson M.; Chen, Irvin S. Y.

doi:10.1016/0092-8674(90)90802-l

Cited by 1,449 publications

(1,301 citation statements)

References 31 publications

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“…From the data in Table 1, HIV replication fold over non-stimulated PBLs at 72 h Syncytia formation in non-stimulated and stimulated PBLs as measured by the infected centers assay (see Materials and methods). a Syncytia/10 4 cells (Stevenson et al, 1990;Zack et al, 1990). In activated T cells, the viral DNA is integrated and HIV replication depends on viral accessory proteins and host factors (Cullen, 1998;Finzi and Silliciano, 1998).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of cyclin T1/CDK9 complexes during T cell activation

et al. 1998

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Cyclin T1 has been identi®ed recently as a regulatory subunit of CDK9 and as a component of the transcription elongation factor P-TEFb. Cyclin T1/CDK9 complexes phosphorylate the carboxy terminal domain (CTD) of RNA polymerase II (RNAP II) in vitro. Here we report that the levels of cyclin T1 are dramatically upregulated by two independent signaling pathways triggered respectively by PMA and PHA in primary human peripheral blood lymphocytes (PBLs). Activation of these two pathways in tandem is su cient for PBLs to enter and progress through the cell cycle. However, the expression of cyclin T1 is not growth and/or cell cycle regulated in other cell types, indicating that regulation of cyclin T1 expression is dependent on tissue-speci®c signaling pathways. Upregulation of cyclin T1 in stimulated PBLs results in induction of the CTD kinase activity of the cyclin T1/CDK9 complex, which in turn correlates directly with phosphorylation of RNAP II in vivo, linking for the ®rst time activation of the cyclin T1/ CDK9 pair with phosphorylation of RNAP II in vivo. In addition, we report here that endogenous CDK9 and cyclin T1 complexes associate with HIV-1 generated Tat in relevant cells and under physiological conditions (HIV-1 infected T cells). This, together with our results showing that HIV-1 replication in stimulated PBLs correlates with the levels of cyclin T1 protein and associated CTD kinase activity, suggests that the cyclin T1/CDK9 pair is one of the HIV-1 required host cellular cofactors generated during T cell activation.

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Section: Discussionmentioning

confidence: 99%

Upregulation of cyclin T1/CDK9 complexes during T cell activation

et al. 1998

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“…The majority of CD4þ T-cells are non-cycling and are resting in the G 0 phase. This phase can restrict early steps in HIV-1 replication including reverse transcription, nuclear import, and integration [Stevenson et al, 1990;Zack et al, 1990;Bukrinsky et al, 1991;Pierson et al, 2002;Swiggard et al, 2004]. However, intact unintegrated DNA may be a significant ''latent'' form of HIV in the resting T-cell [Bukrinsky et al, 1991].…”

Section: Questions Methods and Implicationsmentioning

confidence: 99%

Effects of cell cycle status on early events in retroviral replication

Katz

Greger

Skalka

2005

J of Cellular Biochemistry

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The study of retroviruses over the last century has revealed a wide variety of disease-producing mechanisms, as well as apparently harmless interactions with animal hosts. Despite their potential pathogenic properties, the intrinsic features of retroviruses have been harnessed to create gene transfer vectors that may be useful for the treatment of disease. Retroviruses, as all viruses, have evolved to infect specific cells within the host, and such specificities are relevant to both pathogenesis and retrovirus-based vector design. The majority of cells of an animal host are not progressing rapidly through the cell cycle, and such a cellular environment appears to be suboptimal for replication of all retroviruses. Retrovirus-based vectors can therefore be restricted in many important target cells, such as post-mitotic differentiated cells or stem cells that may divide only infrequently. Despite intense interest, our understanding of how cell cycle status influences retroviral infection is still quite limited. In this review, we focus on the importance of the cell cycle as it relates to the early steps in retroviral replication. Retroviruses have been categorized based on their abilities to complete these early steps in non-cycling cells. However, all retroviruses are subject to a variety of cell cycle restrictions. Here, we discuss such restrictions, and how they may block retroviral replication, be tolerated, or overcome. J. Cell. Biochem. 94: 880-889, 2005. ß 2005 Wiley-Liss, Inc.

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“…PCR was performed on 0.5 mg of total cellular DNA using the M661/ M667 primer pair, which identifies HIV gag DNA. 63 The PCR conditions were previously reported and shown to be semiquantitative. 63 Following PCR, each sample was quantitatively transferred to a 2% agarose gel.…”

Section: Hiv-1 Infection Of Hek-ccr5 Variant Transfectantsmentioning

confidence: 99%

“…63 The PCR conditions were previously reported and shown to be semiquantitative. 63 Following PCR, each sample was quantitatively transferred to a 2% agarose gel. The amount of proviral gag DNA was visualized by ethidium bromide staining.…”

Section: Hiv-1 Infection Of Hek-ccr5 Variant Transfectantsmentioning

confidence: 99%

Variants of CCR5, which are permissive for HIV-1 infection, show distinct functional responses to CCL3, CCL4 and CCL5

et al. 2005

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CCR5 is one of the primary coreceptors for Env-mediated fusion between cells and human immunodeficiency virus type 1 (HIV-1). Analyses of CCR5 variants in cohorts of HIV-1 high-risk individuals led to the identification of multiple single amino-acid substitutions, which may have functional consequences. This study focused on eight naturally occurring allelic variants located between amino-acid residues 60 and 334 of CCR5. All studied allelic variants were highly expressed on the cell surface of HEK-293 cells and permissive for HIV-1 infection. Variant G301V showed 3.5-fold increase in 50% effective concentration (EC 50 ) for CCL4 (MIP 1beta) in a competitive binding assay. There was also a significant reduction in CCL5 (RANTES) EC 50 for the R223Q, A335V and Y339F variants. The most unexpected functional abnormality was exhibited by the R60S variant that exhibited a loss of ligand-induced desensitization in chemotaxis assays, but showed normal CCL4 and CCL5 binding avidity. This mutation is located in the first intracellular loop, a domain that has not previously been shown to be involved in receptor desensitization. In conclusion, our results support earlier studies showing that these naturally occurring point mutations do not limit HIV-1 infection, and indicated that single amino-acid changes can have unexpected functional consequences.

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HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structure

Cited by 1,449 publications

References 31 publications

Upregulation of cyclin T1/CDK9 complexes during T cell activation

Upregulation of cyclin T1/CDK9 complexes during T cell activation

Effects of cell cycle status on early events in retroviral replication

Variants of CCR5, which are permissive for HIV-1 infection, show distinct functional responses to CCL3, CCL4 and CCL5

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