Plasma and Mucosal Fluid from HIV Type 1-Infected Patients But Not from HIV Type 1-Exposed Uninfected Subjects Prevent HIV Type 1-Exposed DC from Infecting Other Target Cells

2007 ◽  
Vol 23 (1) ◽  
pp. 101-106 ◽  
Author(s):  
Johan Söderlund ◽  
Taha Hirbod ◽  
Anna Smed-Sörensen ◽  
Ulrika Johansson ◽  
Joshua Kimani ◽  
...  
Keyword(s):  
Target Cells ◽  
Hiv Type 1 ◽  
Exposed Uninfected

scholarly journals Inactivation of Human Immunodeficiency Virus Type 1 by Porphyrins

2002 ◽  
Vol 46 (12) ◽  
pp. 3917-3925 ◽  
Author(s):  
Andrei N. Vzorov ◽  
Dabney W. Dixon ◽  
Jenna S. Trommel ◽  
Luigi G. Marzilli ◽  
Richard W. Compans
Keyword(s):  
Human Immunodeficiency Virus ◽  
Target Cells ◽  
Copper Chelate ◽  
Active Compounds ◽  
Sexually Transmitted ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Env Protein ◽  
Cd4 Cell

ABSTRACT We have evaluated the anti-human immunodeficiency virus (HIV) activity of a series of natural and synthetic porphyrins to identify compounds that could potentially be used as microbicides to provide a defense against infection by sexually transmitted virus. For assays we used an epithelial HeLa-CD4 cell line with an integrated long terminal repeat-β-galactosidase gene. For structure-activity analysis, we divided the porphyrins tested into three classes: (i) natural porphyrins, (ii) metallo-tetraphenylporphyrin tetrasulfonate (metallo-TPPS4) derivatives, and (iii) sulfonated tetra-arylporphyrin derivatives. None of the natural porphyrins studied reduced infection by more than 80% at a concentration of 5 μg/ml in these assays. Some metal chelates of TPPS4 were more active, and a number of sulfonated tetra-aryl derivatives showed significantly higher activity. Some of the most active compounds were the sulfonated tetranaphthyl porphyrin (TNapPS), sulfonated tetra-anthracenyl porphyrin (TAnthPS), and sulfonated 2,6-difluoro-meso-tetraphenylporphine [TPP(2,6-F2)S] and its copper chelate [TPP(2,6-F2)S,Cu], which reduced infection by 99, 96, 94, and 96%, respectively. Our observations indicate that at least some of these compounds are virucidal, i.e., that they render the virus noninfectious. The active compounds were found to inhibit binding of the HIV type 1 gp120 to CD4 and also to completely inhibit the ability of Env proteins expressed from recombinant vectors to induce cell fusion with receptor-bearing target cells. These results support the conclusion that modified porphyrins exhibit substantial activity against HIV and that their target is the HIV Env protein.

scholarly journals Coreceptor Competition for Association with CD4 May Change the Susceptibility of Human Cells to Infection with T-Tropic and Macrophagetropic Isolates of Human Immunodeficiency Virus Type 1

2000 ◽  
Vol 74 (11) ◽  
pp. 5016-5023 ◽  
Author(s):  
Shirley Lee ◽  
Cheryl K. Lapham ◽  
Hong Chen ◽  
Lisa King ◽  
Jody Manischewitz ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Chemokine Receptors ◽  
Target Cells ◽  
Primary Cells ◽  
Susceptibility To Infection ◽  
Immunodeficiency Virus ◽  
N Terminus ◽  
Hiv Type 1

ABSTRACT The chemokine receptors CCR5 and CXCR4 were found to function in vivo as the principal coreceptors for M-tropic and T-tropic human immunodeficiency virus (HIV) strains, respectively. Since many primary cells express multiple chemokine receptors, it was important to determine if the efficiency of virus-cell fusion is influenced not only by the presence of the appropriate coreceptor (CXCR4 or CCR5) but also by the levels of other coreceptors expressed by the same target cells. We found that in cells with low to medium surface CD4 density, coexpression of CCR5 and CXCR4 resulted in a significant reduction in the fusion with CXCR4 domain (X4) envelope-expressing cells and in their susceptibility to infection with X4 viruses. The inhibition could be reversed either by increasing the density of surface CD4 or by antibodies against the N terminus and second extracellular domains of CCR5. In addition, treatment of macrophages with a combination of anti-CCR5 antibodies or β-chemokines increased their fusion with X4 envelope-expressing cells. Conversely, overexpression of CXCR4 compared with CCR5 inhibited CCR5-dependent HIV-dependent fusion in 3T3.CD4.401 cells. Thus, coreceptor competition for association with CD4 may occur in vivo and is likely to have important implications for the course of HIV type 1 infection, as well as for the outcome of coreceptor-targeted therapies.

scholarly journals Differential Pathogenesis of Primary CCR5-Using Human Immunodeficiency Virus Type 1 Isolates in Ex Vivo Human Lymphoid Tissue

2005 ◽  
Vol 79 (17) ◽  
pp. 11151-11160 ◽  
Author(s):  
Ingrid Karlsson ◽  
Jean-Charles Grivel ◽  
Silvia Sihui Chen ◽  
Anders Karlsson ◽  
Jan Albert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Infected Individual ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Tissue Factors ◽  
Hiv Type 1 ◽  
Hiv 1

ABSTRACT In the course of human immunodeficiency virus (HIV) disease, CCR5-utilizing HIV type 1 (HIV-1) variants (R5), which typically transmit infection and dominate its early stages, persist in approximately half of the infected individuals (nonswitch virus patients), while in the other half (switch virus patients), viruses using CXCR4 (X4 or R5X4) emerge, leading to rapid disease progression. Here, we used a system of ex vivo tonsillar tissue to compare the pathogeneses of sequential primary R5 HIV-1 isolates from patients in these two categories. The absolute replicative capacities of HIV-1 isolates seemed to be controlled by tissue factors. In contrast, the replication level hierarchy among sequential isolates and the levels of CCR5+ CD4+ T-cell depletion caused by the R5 isolates seemed to be controlled by viral factors. R5 viruses isolated from nonswitch virus patients depleted more target cells than R5 viruses isolated from switch virus patients. The high depletion of CCR5+ cells by HIV-1 isolates from nonswitch virus patients may explain the steady decline of CD4+ T cells in patients with continuous dominance of R5 HIV-1. The level of R5 pathogenicity, as measured in ex vivo lymphoid tissue, may have a predictive value reflecting whether, in an infected individual, X4 HIV-1 will eventually dominate.

scholarly journals Truncation of the Membrane-Spanning Domain of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Defines Elements Required for Fusion, Incorporation, and Infectivity

2009 ◽  
Vol 83 (22) ◽  
pp. 11588-11598 ◽  
Author(s):  
Ling Yue ◽  
Liang Shang ◽  
Eric Hunter
Keyword(s):  
Amino Acids ◽  
Target Cells ◽  
Amino Acid Residues ◽  
Hydrophobic Residues ◽  
Head Groups ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Membrane Spanning ◽  
Hiv 1

ABSTRACT The membrane-spanning domain (MSD) of the envelope (Env) glycoprotein from human (HIV) and simian immunodeficiency viruses plays a key role in anchoring the Env complex into the viral membrane but also contributes to its biological function in fusion and virus entry. In HIV type 1 (HIV-1), it has been predicted to span 27 amino acids, from lysine residue 681 to arginine 707, and encompasses an internal arginine at residue 694. By examining a series of C-terminal-truncation mutants of the HIV-1 gp41 glycoprotein that substituted termination codons for amino acids 682 to 708, we show that this entire region is required for efficient viral infection of target cells. Truncation to the arginine at residue 694 resulted in an Env complex that was secreted from the cells. In contrast, a region from residues 681 to 698, which contains highly conserved hydrophobic residues and glycine motifs and extends 4 amino acids beyond 694R, can effectively anchor the protein in the membrane, allow efficient transport to the plasma membrane, and mediate wild-type levels of cell-cell fusion. However, these fusogenic truncated Env mutants are inefficiently incorporated into budding virions. Based on the analysis of these mutants, a “snorkeling” model, in which the flanking charged amino acid residues at 681 and 694 are buried in the lipid while their side chains interact with polar head groups, is proposed for the HIV-1 MSD.

scholarly journals HLA Class I and KIR Genes Do Not Protect Against HIV Type 1 Infection in Highly Exposed Uninfected Individuals With Hemophilia A

2014 ◽  
Vol 210 (7) ◽  
pp. 1047-1051 ◽  
Author(s):  
Nicolas Vince ◽  
Arman A. Bashirova ◽  
Alexandra Lied ◽  
Xiaojiang Gao ◽  
Lucy Dorrell ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Hla Class I ◽  
Class I ◽  
Kir Genes ◽  
Hiv Type 1 ◽  
Exposed Uninfected
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