Identification of a novel human immunodeficiency virus strain cytopathic to megakaryocytic cells

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3336-3342 ◽  
Author(s):  
MS Kunzi ◽  
JE Groopman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Entry ◽  
Envelope Protein ◽  
Severe Thrombocytopenia ◽  
Cell Tropism ◽  
Intracellular Replication ◽  
Gp120 Envelope ◽  
Human Immunodeficiency Virus Strain ◽  
Immunodeficiency Virus ◽  
Hiv Gp120

Abstract Impaired megakaryocytopoiesis may be a contributing factor to thrombocytopenia associated with human immunodeficiency virus (HIV) infection. Because HIV isolates differ in their host range and pathogenicity, we investigated whether HIV strains with demonstrable cell tropism and increased cytopathicity for megakaryocytes could be derived from the blood of thrombocytopenic HIV-infected individuals. We derived a strain, HIV-WW, from the peripheral blood of an individual with severe thrombocytopenia and found the virus to be highly and specifically cytotoxic to CMK and DAMI megakaryocytic cells. CMK and DAMI cells were not permissive for the virus and HIV-WW induced cytopathicity for these megakaryocytic cells did not depend on viral replication. The CD4 N-terminus-binding domain of the HIV gp120 envelope protein did not appear to be involved in determining the cytopathic phenomenon. HIV may impair megakaryocytopoiesis through interactions at the cell surface in some cases rather than through viral entry and intracellular replication.

scholarly journals Identification of a novel human immunodeficiency virus strain cytopathic to megakaryocytic cells

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3336-3342
Author(s):  
MS Kunzi ◽  
JE Groopman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Entry ◽  
Envelope Protein ◽  
Severe Thrombocytopenia ◽  
Cell Tropism ◽  
Intracellular Replication ◽  
Gp120 Envelope ◽  
Human Immunodeficiency Virus Strain ◽  
Immunodeficiency Virus ◽  
Hiv Gp120

Impaired megakaryocytopoiesis may be a contributing factor to thrombocytopenia associated with human immunodeficiency virus (HIV) infection. Because HIV isolates differ in their host range and pathogenicity, we investigated whether HIV strains with demonstrable cell tropism and increased cytopathicity for megakaryocytes could be derived from the blood of thrombocytopenic HIV-infected individuals. We derived a strain, HIV-WW, from the peripheral blood of an individual with severe thrombocytopenia and found the virus to be highly and specifically cytotoxic to CMK and DAMI megakaryocytic cells. CMK and DAMI cells were not permissive for the virus and HIV-WW induced cytopathicity for these megakaryocytic cells did not depend on viral replication. The CD4 N-terminus-binding domain of the HIV gp120 envelope protein did not appear to be involved in determining the cytopathic phenomenon. HIV may impair megakaryocytopoiesis through interactions at the cell surface in some cases rather than through viral entry and intracellular replication.

scholarly journals Human immunodeficiency virus type 1 gp120 envelope characteristics associated with disease progression differ in family members infected with genetically similar viruses

2013 ◽  
Vol 94 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Elly Baan ◽  
Renée M. van der Sluis ◽  
Margreet E. Bakker ◽  
Vincent Bekker ◽  
Dasja Pajkrt ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Positive Charge ◽  
Gp120 Envelope ◽  
Immunodeficiency Virus ◽  
Virus Strains ◽  
Hiv 1

The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.

scholarly journals Inhibition of Human Immunodeficiency Virus Replication by a Dual CCR5/CXCR4 Antagonist

2004 ◽  
Vol 78 (23) ◽  
pp. 12996-13006 ◽  
Author(s):  
Katrien Princen ◽  
Sigrid Hatse ◽  
Kurt Vermeire ◽  
Stefano Aquaro ◽  
Erik De Clercq ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Entry ◽  
Mononuclear Cells ◽  
Human Immunodeficiency Virus Replication ◽  
Cxcr4 Antagonist ◽  
Peripheral Blood Mononuclear ◽  
Transfected Cells ◽  
Immunodeficiency Virus ◽  
Intracellular Ca ◽  
Hiv 1

ABSTRACT Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC50] ranging from 1.2 to 26.5 μM) in various T-cell lines, CCR5- or CXCR4-transfected cells, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages. AMD3451 also inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC50, 1.8 to 7.3 μM). A PCR-based viral entry assay revealed that AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca2+ signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca2+ flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did not interfere with chemokine-induced Ca2+ signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca2+ signaling by itself at concentrations up to 400 μM. In freshly isolated monocytes, AMD3451 inhibited the Ca2+ flux induced by CXCL12 and CCL4 but not that induced by CCL2, CCL3, CCL5, and CCL7. The CXCL12- and CCL3-induced chemotaxis was also dose-dependently inhibited by AMD3451. Furthermore, AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells. AMD3451, in contrast to the specific CXCR4 antagonist AMD3100, did not inhibit but enhanced the binding of several anti-CXCR4 monoclonal antibodies (such as clone 12G5) at the cell surface, pointing to a different interaction with CXCR4. AMD3451 is the first low-molecular-weight anti-HIV agent with selective HIV coreceptor, CCR5 and CXCR4, interaction.

scholarly journals Safety and Pharmacokinetics of Intravaginal Rings Delivering Tenofovir in Pig-Tailed Macaques

2012 ◽  
Vol 56 (11) ◽  
pp. 5952-5960 ◽  
Author(s):  
John A. Moss ◽  
Amanda M. Malone ◽  
Thomas J. Smith ◽  
Irina Butkyavichene ◽  
Cassandra Cortez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Tissue Concentration ◽  
Clinical Investigation ◽  
Drug Loading ◽  
Transcriptase Inhibitor ◽  
Vaginal Tissue ◽  
Macaque Model ◽  
Intravaginal Rings ◽  
Human Immunodeficiency Virus Strain ◽  
Immunodeficiency Virus

ABSTRACTAntiretroviral-based microbicides applied topically to the vagina may play an important role in protecting women from HIV infection. Incorporation of the nucleoside reverse transcriptase inhibitor tenofovir (TFV) into intravaginal rings (IVRs) for sustained mucosal delivery may lead to increased microbicide product adherence and efficacy compared with those of conventional vaginal formulations. Formulations of a novel “pod IVR” platform spanning a range of IVR drug loadings and daily release rates of TFV were evaluated in a pig-tailed macaque model. The rings were safe and exhibited sustained release at controlled rates over 28 days. Vaginal secretion TFV levels were independent of IVR drug loading and were able to be varied over 1.5 log units by changing the ring configuration. Mean TFV levels in vaginal secretions were 72.4 ± 109 μg ml−1(slow releasing) and 1.84 ± 1.97 mg ml−1(fast releasing). The mean TFV vaginal tissue concentration from the slow-releasing IVRs was 76.4 ± 54.8 μg g−1and remained at steady state 7 days after IVR removal, consistent with the long intracellular half-life of TFV. Intracellular tenofovir diphosphate (TFV-DP), the active moiety in defining efficacy, was measured in vaginal lymphocytes collected in the study using the fast-releasing IVR formulation. Mean intracellular TFV-DP levels of 446 ± 150 fmol/106cells fall within a range that may be protective of simian-human immunodeficiency virus strain SF162p3 (SHIVSF162p3) infection in nonhuman primates. These data suggest that TFV-releasing IVRs based on the pod design have potential for the prevention of transmission of human immunodeficiency virus type 1 (HIV-1) and merit further clinical investigation.

scholarly journals Use of Coreceptors Other Than CCR5 by Non-Syncytium-Inducing Adult and Pediatric Isolates of Human Immunodeficiency Virus Type 1 Is Rare In Vitro

1998 ◽  
Vol 72 (11) ◽  
pp. 9337-9344 ◽  
Author(s):  
Yi-jun Zhang ◽  
Tatjana Dragic ◽  
Yunzhen Cao ◽  
Leondios Kostrikis ◽  
Douglas S. Kwon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Entry ◽  
Infected Infant ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We have tested a panel of pediatric and adult human immunodeficiency virus type 1 (HIV-1) primary isolates for the ability to employ the following proteins as coreceptors during viral entry: CCR1, CCR2b, CCR3, CCR4, CCR5, CCR8, CXCR4, Bonzo, BOB, GPR1, V28, US28, and APJ. Most non-syncytium-inducing isolates could utilize only CCR5. All syncytium-inducing viruses used CXCR4, some also employed V28, and one (DH123) used CCR8 and APJ as well. A longitudinal series of HIV-1 subtype B isolates from an infected infant and its mother utilized Bonzo efficiently, as well as CCR5. The maternal isolates, which were syncytium inducing, also used CXCR4, CCR8, V28, and APJ.

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