scholarly journals DC-SIGN Interactions with Human Immunodeficiency Virus: Virus Binding and Transfer Are Dissociable Functions

2001 ◽  
Vol 75 (21) ◽  
pp. 10523-10526 ◽  
Author(s):  
Stefan Pöhlmann ◽  
George J. Leslie ◽  
Terri G. Edwards ◽  
Todd Macfarlan ◽  
Jacqueline D. Reeves ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Underlying Mechanism ◽  
Virus Binding ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Virus

ABSTRACT The C-type lectins DC-SIGN and DC-SIGNR capture and transfer human immunodeficiency virus (HIV) to susceptible cells, although the underlying mechanism is unclear. Here we show that DC-SIGN/DC-SIGNR-mediated HIV transmission involves dissociable binding and transfer steps, indicating that efficient virus transmission is not simply due to tethering of virus to the cell surface.

scholarly journals Association of Selected Phenotypic Markers of Lymphocyte Activation and Differentiation with Perinatal Human Immunodeficiency Virus Transmission and Infant Infection

2005 ◽  
Vol 12 (5) ◽  
pp. 622-631 ◽  
Author(s):  
John S. Lambert ◽  
Jack Moye ◽  
Susan F. Plaeger ◽  
E. Richard Stiehm ◽  
James Bethel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Lymphocyte Activation ◽  
Phenotypic Markers ◽  
Perinatal Hiv ◽  
Hla Dr ◽  
Increased Risk ◽  
Immunodeficiency Virus

ABSTRACT This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4+ T cells. Most notably, levels of total CD8+ T cells and CD8+ CD38+ cells made significant independent contributions to predicting the risk of mother-to-child transmission. Adjusting for HIV-1 RNA level at entry, a one percentage-point increase in these marker combinations was associated with a nine percent increase in the likelihood of maternal transmission. Total as well as naïve CD4+ T cells were significantly higher in uninfected than infected infants. Total CD8+ cells, as well as CD8+cells positive for HLA-DR+, CD45 RA+ HLA-DR+, and CD28+ HLA-DR+ were elevated in infected infants. Detailed immunophenotyping may be helpful in predicting which pregnant HIV-infected women are at increased risk of transmitting HIV to their infants. Increasing differences in lymphocyte subsets between infected and uninfected infants became apparent as early as six weeks of age. Detailed immunophenotyping may be useful in supporting the diagnosis of HIV infection in infants with perinatal HIV exposure.

scholarly journals Implementation of Syringe Services Programs to Prevent Rapid Human Immunodeficiency Virus Transmission in Rural Counties in the United States: A Modeling Study

2019 ◽  
Vol 70 (6) ◽  
pp. 1096-1102 ◽  
Author(s):  
William C Goedel ◽  
Maximilian R F King ◽  
Mark N Lurie ◽  
Sandro Galea ◽  
Jeffrey P Townsend ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Hiv Infections ◽  
The United States ◽  
Single Infection ◽  
Agent Based ◽  
Immunodeficiency Virus ◽  
Barriers To Implementation ◽  
Scott County

Abstract Background Syringe services programs (SSPs) are effective venues for delivering harm-reduction services to people who inject drugs (PWID). However, SSPs often face significant barriers to implementation, particularly in the absence of known human immunodeficiency virus (HIV) outbreaks. Methods Using an agent-based model, we simulated HIV transmission in Scott County, Indiana, a rural county with a 1.7% prevalence of injection drug use. We compared outcomes arising in the absence of an SSP, in the presence of a pre-existing SSP, and with implementation of an SSP after the detection of an HIV outbreak among PWID over 5 years following the introduction of a single infection into the network. Results In the absence of an SSP, the model predicted an average of 176 infections among PWID over 5 years or an incidence rate of 12.1/100 person-years. Proactive implementation averted 154 infections and decreased incidence by 90.3%. With reactive implementation beginning operations 10 months after the first infection, an SSP would prevent 107 infections and decrease incidence by 60.8%. Reductions in incidence were also observed among people who did not inject drugs. Conclusions Based on model predictions, proactive implementation of an SSP in Scott County had the potential to avert more HIV infections than reactive implementation after the detection of an outbreak. The predicted impact of reactive SSP implementation was highly dependent on timely implementation after detecting the earliest infections. Consequently, there is a need for expanded proactive SSP implementation in the context of enhanced monitoring of outbreak vulnerability in Scott County and similar rural contexts.

scholarly journals Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and gp120 Dependent and Requires Cell Surface Heparans

1998 ◽  
Vol 72 (5) ◽  
pp. 3623-3634 ◽  
Author(s):  
Isabelle Mondor ◽  
Sophie Ugolini ◽  
Quentin J. Sattentau
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Hela Cells ◽  
Target Cells ◽  
Cd4 Cells ◽  
Virus Binding ◽  
Hla Dr ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The binding of human immunodeficiency virus type 1 (HIV-1) (Hx10) virions to two different cell lines was analyzed by using a novel assay based on the detection, by anti-HLA-DR-specific antibodies, of HLA-DR+ virus binding to HLA-DR− cells. Virion attachment to the CD4+-T-cell line A3.01 was highly CD4 dependent in that it was potently inhibited by CD4 monoclonal antibodies (MAbs), and little virus binding to the CD4−sister A2.01 line was observed. By contrast, virion binding to HeLa cells expressing moderate or high levels of CD4 was equivalent to, or lower than, binding to wild-type CD4− HeLa cells. Moreover, several CD4 MAbs did not reduce, but enhanced, HIV-1 attachment to HeLa-CD4 cells. CD4 was required for infection of HeLa cells, however, demonstrating a postattachment role for this receptor. MAbs specific for the V2 and V3 loops and the CD4i epitope of gp120 strongly inhibited virion binding to HeLa-CD4 cells, whereas MAbs specific for the CD4bs and the 2G12 epitopes enhanced attachment. Despite this, all gp120- and gp41-specific MAbs tested neutralized infectivity on HeLa-CD4 cells. HIV-1 attachment to HeLa cells was only partially inhibited by MAbs specific for adhesion molecules present on the virus or target cells but was completely blocked by polyanions such as heparin, dextran sulfate, and pentosan sulfate. Treatment of HeLa-CD4 cells with heparinases completely eliminated HIV attachment and infection, strongly implicating cell surface heparans in the attachment process. CD4 dependence for HIV-1 attachment to target cells is thus highly cell line specific and may be replaced by other ligand-receptor interactions.

scholarly journals DC-SIGN Interactions with Human Immunodeficiency Virus Type 1 and 2 and Simian Immunodeficiency Virus

2001 ◽  
Vol 75 (10) ◽  
pp. 4664-4672 ◽  
Author(s):  
Stefan Pöhlmann ◽  
Frédéric Baribaud ◽  
Benhur Lee ◽  
George J. Leslie ◽  
Melissa D. Sanchez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Lectin Binding ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Virus Binding ◽  
Expression Levels ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Dendritic cells (DCs) efficiently bind and transmit human immunodeficiency virus (HIV) to cocultured T cells and so may play an important role in HIV transmission. DC-SIGN, a novel C-type lectin that is expressed in DCs, has recently been shown to bind R5 HIV type 1 (HIV-1) strains and a laboratory-adapted X4 strain. To characterize the interaction of DC-SIGN with primate lentiviruses, we investigated the structural determinants of DC-SIGN required for virus binding and transmission to permissive cells. We constructed a panel of DC-SIGN mutants and established conditions which allowed comparable cell surface expression of all mutants. We found that R5, X4, and R5X4 HIV-1 isolates as well as simian immunodeficiency and HIV-2 strains bound to DC-SIGN and could be transmitted to CD4/coreceptor-positive cell types. DC-SIGN contains a single N-linked carbohydrate chain that is important for efficient cell surface expression but is not required for DC-SIGN-mediated virus binding and transmission. In contrast, C-terminal deletions removing either the lectin binding domain or the repeat region abrogated DC-SIGN function. Trypsin-EDTA treatment inhibited DC-SIGN mediated infection, indicating that virus was maintained at the surface of the DC-SIGN-expressing cells used in this study. Finally, quantitative fluorescence-activated cell sorting analysis of AU1-tagged DC-SIGN revealed that the efficiency of virus transmission was strongly affected by variations in DC-SIGN expression levels. Thus, variations in DC-SIGN expression levels on DCs could greatly affect the susceptibility of human individuals to HIV infection.

scholarly journals Natural and iatrogenic factors in human immunodeficiency virus transmission

2001 ◽  
Vol 356 (1410) ◽  
pp. 947-953 ◽  
Author(s):  
Robin A. Weiss
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Oral Polio Vaccine ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Immunodeficiency Virus ◽  
Cast Doubt ◽  
One Year ◽  
Iatrogenic Transmission

In the light of the evidence and discussion presented during The Royal Society Discussion Meeting it seems to me that the oral polio vaccine (OPV) hypothesis for the origins of human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome epidemic is less tenable now than one year earlier. The OPV hypothesis does not accord with HIV phylogenetic studies: the geographical correlation has been challenged; the testimony of those directly involved with OPV trial vaccines denies the use of chimpanzees, corroborating tests on the still–available vials of the CHAT vaccines, which contain neither simian immunodeficiency virus nor chimpanzee DNA. Yet one lesson to be learned from considering OPV as a source of HIV is how plausibly it might have happened and how cautious we need to be over introducing medical treatments derived from animal tissues, such as live, attenuated vaccines or xenotransplantation. To cast doubt on the OPV hypothesis is not to dismiss entirely the role of iatrogenic factors in HIV transmission from chimpanzees in the first instance, in HIV adaptation to onward transmission during its early phase in humans, or in the later spread of HIV to patients, for example, with haemophilia. To reduce the argument over the origins of HIV to the ‘OPV hypothesis’ versus the ‘cut–hunter hypothesis’ is an oversimplistic and false antithesis. Both natural and iatrogenic transmission of many retroviruses, including HIV, have been thoroughly documented and are not mutually exclusive. Exactly how, when and where the first human(s) became infected with the progenitor of HIV–1 group M, which gave rise to the pandemic strain, is likely, however, to remain a matter of conjecture.

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