Recruitment of a protein complex containing Tat and cyclin T1 to TAR governs the species specificity of HIV-1 Tat

Bieniasz, Paul D.; Grdina, Therese A.; Bogerd, Hal P.; Cullen, Bryan R.

doi:10.1093/emboj/17.23.7056

Cited by 241 publications

(290 citation statements)

References 44 publications

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“…CycK and CycT1 have 53 identical residues in the cyclin homology box domain, which is responsible for binding to CDK9 (44); hence, the possibility of competition between CycK and CycT1 for binding to CDK9 cannot be ruled out. The Tat-interacting region, also known as the Tat-responsive motif, located outside the cyclin homology box of CycT1, is not present in CycK (49,50), and thus a possible role of the CDK9-CycK complex in modulating HIV-1 transcription can be ruled out. To function as a part of an active P-TEFb complex for HIV-1 gene transcription, CDK9 needs to be translocated into the nucleus, and it shuttles between the nucleus and cytoplasm under the influence of CycT1 levels in the cell (47).…”

Section: Discussionmentioning

confidence: 99%

Cyclin K Inhibits HIV-1 Gene Expression and Replication by Interfering with Cyclin-dependent Kinase 9 (CDK9)-Cyclin T1 Interaction in Nef-dependent Manner

Khan

Mitra

2011

Journal of Biological Chemistry

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Human immunodeficiency virus type-1 (HIV-1) perpetuates its survival in the host by utilizing multiple strategies such as irreversible integration of its DNA into the host cell genome to establish the provirus (1), diversification of its genome to escape or tolerate adaptive immune responses (2), and use of the accessory genes (nef, vif, vpu, and vpr) to modulate host cell immune responses further (3-5). These viral accessory genes are frequently seen as dispensable in many in vitro cell culture systems but seem to be indispensable, in the context of natural infections in vivo. Among these accessory genes, pleiotropic functions of Nef have been studied extensively. It is a 27-30-kDa, N-terminally myristoylated protein having a well characterized CD4 down-regulatory activity (6). Nef does not possess any enzymatic activity, but it modulates diverse signaling pathways and the gene expression of host cell proteins (7,8). Furthermore, Nef influences the activation state of the host cell by bringing together different host cell proteins, protein kinases, and components of the endocytic machinery and making the cells permissible to the virus (9, 10). All these functions of Nef are manifested by a number of events such as activation of signaling molecules, modulation of apoptosis, activation of transcription factors, mitigation of transcriptional repressors, and an increase in the infectivity of virions (11). Although these functions of Nef have been well studied, controversy exists on its role in viral infectivity and replication as both negative (12, 13) and positive (14, 15) roles have been attributed in the literature. Although a number of reports show that Nef increases viral replication by activating T-cells, the molecular basis of Nef-induced viral gene expression and replication remains to be clearly elucidated. Nef was also shown to physically interact with Tat and augment viral gene expression (16), although availability of Tat is critical for the elongation step of long terminal repeat (LTR) 2 -driven transcription by RNA polymerase II. Several cellular factors have been identified for their roles in this process, including positive transcription elongation factor b (P-TEFb) complex. Different P-TEFb complexes isolated from mammalian cells contain a common catalytic subunit, cyclin-dependent kinase 9 (CDK9), and one of the regulatory cyclins, CycT1, CycT2a, CycT2b,. However, CycT1-containing P-TEFb complex is the key complex responsible for HIV-1 transcription elongation (19). Tat is expressed early in the replicative cycle of HIV and is essential for viral gene expression from the LTR promoter. It recognizes the 5Ј-bulge in the transactivation response stem loop RNA, which is located at the 5Ј-end of all viral transcripts. Tat binds to CycT1, and together they form the combinatorial surface that interacts with the transactivation response RNA with high affinity and specificity. The obligate partner of CycT1, CDK9, then hyperphosphorylates the C-terminal domain (CTD) of RNA polymerase II, resulting in incre...

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Section: Discussionmentioning

confidence: 99%

Cyclin K Inhibits HIV-1 Gene Expression and Replication by Interfering with Cyclin-dependent Kinase 9 (CDK9)-Cyclin T1 Interaction in Nef-dependent Manner

Khan

Mitra

2011

Journal of Biological Chemistry

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“…Because mammalian genomes encode proteins that are polymorphic between species, plasticity of viral genomes is required for viruses to expand their host range. The lentiviral Tat gene is similarly adapted to a species-specific interaction with its cellular cofactor cyclin-T1 (30). For SIV to replicate in the various primate species, Vif had to accommodate the differences at amino acid 128 of APOBEC3G.…”

Section: Discussionmentioning

confidence: 99%

A single amino acid of APOBEC3G controls its species-specific interaction with virion infectivity factor (Vif)

Schröfelbauer

Chen

Landau

2004

Proc. Natl. Acad. Sci. U.S.A.

298

305

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The virion infectivity factor (Vif) accessory protein of HIV-1 forms a complex with the cellular cytidine deaminase APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) to block its antiviral activity. The antiviral property of APOBEC3G is conserved in several mammalian species, but the ability of Vif to block this activity is species-specific. HIV-1 Vif blocks human APOBEC3G but does not block the mouse or African green monkey (AGM) enzyme. Conversely, SIVAGM Vif blocks the antiviral activity of AGM but not human APOBEC3G. We demonstrate that the species specificity is caused by a single amino acid difference in APOBEC3G. Replacement of Asp-128 in human APOBEC3G with the Lys-128 of AGM APOBEC3G caused the enzyme to switch its interaction, becoming sensitive to SIVAGM Vif and resistant to HIV-1 Vif. Conversely, the reciprocal Lys to Asp switch in AGM APOBEC3G reversed its specificity for Vif. The reversal of biological activity was accompanied by the corresponding switch in the species specificity with which the enzyme physically associated with Vif and was excluded from virions. The charge of the amino acid at position 128 was a critical determinant of species specificity. Based on the crystal structure of the distantly related Escherichia coli cytidine deaminase, we propose that this amino acid is positioned on a solvent-exposed loop of APOBEC3G on the same face of the protein as the catalytic site.

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“…Another block in the retroviral cycle has been elucidated due to the inability of HIV to replicate in mouse cells that are made fully permissive to viral entry. The block in this case is located after integration and caused by the inability of the mouse cyclin T1 to form a functional complex with HIV Tat (Bieniasz et al, 1998). Several other preintegration and postbinding/post-entry blocks limiting retroviral tropism have been identified for several retroviruses (Nisole and Saib, 2004).…”

Section: Cell Type-specific Pathogenesis Versus Tropismmentioning

confidence: 99%

HTLV-1 tropism and envelope receptor

et al. 2005

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The identification of CD4 as the primary receptor for HIV followed shortly after the discovery of the virus, but the HTLV receptor remained long elusive, until its recent identification as the GLUT1 glucose transporter. In the present review, we describe the status of the literature that surrounded this discovery as well as the in vitro and in vivo observations that led to the identification of GLUT1. Also, we will explore a few tracks to conciliate the in vitro and in vivo data on HTLV-1 tropism within the context of the HTLV literature that has accumulated over the past 25 years. A close examination of these data leads us to conclude that the preferential detection of HTLV-1 in CD4 þ T lymphocyte subsets in vivo, even in the absence of leukemia, is not likely to be directly related to envelope receptor interactions, but rather to an array of postentry selection bottlenecks in vivo. Furthermore, we propose that infection of other hematopoietic and nonhematopoietic cells is likely to take place during the lifetime of an individual, with a burst early during the infection. Oncogene (2005) 24, 6016-6025.

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Recruitment of a protein complex containing Tat and cyclin T1 to TAR governs the species specificity of HIV-1 Tat

Cited by 241 publications

References 44 publications

Cyclin K Inhibits HIV-1 Gene Expression and Replication by Interfering with Cyclin-dependent Kinase 9 (CDK9)-Cyclin T1 Interaction in Nef-dependent Manner

Cyclin K Inhibits HIV-1 Gene Expression and Replication by Interfering with Cyclin-dependent Kinase 9 (CDK9)-Cyclin T1 Interaction in Nef-dependent Manner

A single amino acid of APOBEC3G controls its species-specific interaction with virion infectivity factor (Vif)

HTLV-1 tropism and envelope receptor

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