Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti–HIV-1 IgG without induction of maturation

Holl, Vincent; Peressin, Maryse; Schmidt, Sylvie; Decoville, Thomas; Zolla‐Pazner, Susan; Aubertin, Anne-Marie; Moog, Christiane

doi:10.1182/blood-2005-08-3490

Cited by 56 publications

(67 citation statements)

References 63 publications

(87 reference statements)

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“…Blocking experiments confirmed the importance of Fc␥-R engagement by 2F5 in inhibiting HIV replication in MDDC-T cell cocultures. These data are in agreement with previous studies showing 2F5 IgG as highly active in preventing HIV-1 infection of immature MDM and MDDCs relative to 2F5 Fab (25)(26)(27)57) and the importance of Fc␥-R engagement in reducing DC-mediated trans-infection of CD4 T cells (58). Interestingly, the inhibitory activities (IC 50 ) of 2F5 IgG and Fab were similar in cervical explant cultures despite such tissue containing a high density of macrophages and dendritic cells.…”

Section: Discussionsupporting

confidence: 82%

“…Previous studies have demonstrated that 2F5 IgG can provide potent Fc-mediated inhibition of HIV infection of antigen-presenting cells prevalent in mucosal tissues, including macrophages, dendritic cells (DCs), and Langerhan's cells. Although initially thought to be mediated by phagocytosis and degradation of opsonized viral particles (25)(26)(27), more recent data have suggested that binding to Fc␥RI provides a kinetic advantage for accessing partially cryptic epitopes, such as that recognized by 2F5 that is independent of phagocytosis (28). Additional Fc-mediated activity includes antibody-dependent cellular cytotoxicity (ADCC) (29) and antibody-dependent cellular viral inhibition (ADCVI) (8), potentially leading to killing of infected cells.…”

mentioning

confidence: 99%

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Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

Klein

Veazey

Warrier

et al. 2013

J Virol

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

Klein

Veazey

Warrier

et al. 2013

J Virol

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“…The nonneutralizing Abs induced in the early acute phase of infection have been associated with control of viral load via complement virion lysis, while NAbs appear later in disease. Moreover, both types of Ab inhibit HIV-1 replication in iDCs, thereby preventing transmission of de novo produced HIV-1 (15,16). Despite the high variation in the Ab repertoire only a few broadly NAbs directed against the gp41 region, Abs 2F5 and 4E10 (27,34,35,46,55), or the gp120 envelope region, Abs 2G12 and b12 (2,42), have been found to efficiently block HIV-1 target cell infection.…”

Section: Human Immunodeficiency Virus Type 1 (Hiv-1) Primarily Infectmentioning

confidence: 99%

Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4⁺T Lymphocytes intrans

Montfort

Thomas

Pollakis

et al. 2008

J Virol

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Human immunodeficiency virus type 1 (HIV-1) preferentially utilizes the CCR5 coreceptor for target cell entry in the acute phase of infection, while later in disease progression the virus switches to the CXCR4 coreceptor in approximately 50% of patients. In response to HIV-1 the adaptive immune response is triggered, and antibody (Ab) production is elicited to block HIV-1 entry. We recently determined that dendritic cells (DCs) can efficiently capture Ab-neutralized HIV-1, restore infectivity, and transmit infectious virus to target cells. Here, we tested the effect of Abs on trans transmission of CCR5 or CXCR4 HIV-1 variants. We observed that transmission of HIV-1 by immature as well as mature DCs was significantly higher for CXCR4-than CCR5-tropic viral strains. Additionally, neutralizing Abs directed against either the gp41 or gp120 region of the envelope such as 2F5, 4E10, and V3-directed Abs inhibited transmission of CCR5-tropic HIV-1, whereas Ab-treated CXCR4-tropic virus demonstrated unaltered or increased transmission. To further study the effects of coreceptor usage we tested molecularly cloned HIV-1 variants with modifications in the envelope that were based on longitudinal gp120 V1 and V3 variable loop sequences from a patient progressing to AIDS. We observed that DCs preferentially facilitated infection of CD4 ؉ T lymphocytes of viral strains with an envelope phenotype found late in disease. Taken together, our results illustrate that DCs transmit CXCR4-tropic HIV-1 much more efficiently than CCR5 strains; we hypothesize that this discrimination could contribute to the in vivo coreceptor switch after seroconversion and could be responsible for the increase in viral load.

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“…HIV-1 transmission in cis is characterized by direct infection of the DC, which takes a few days, resulting in transfer of de novo-produced virions (9,10). DC-mediated HIV-1 transmission in trans relies on the capture of HIV-1 particles, followed by transfer to HIV-1-susceptible CD4 cells.…”

mentioning

confidence: 99%

Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

Montfort

Thomas

Krawczyk

et al. 2015

The Journal of Immunology

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Ab-neutralized HIV-1 can be captured by dendritic cells (DCs), which subsequently transfer infectious HIV-1 to susceptible CD4+ T cells. In this study, we examined the capacity of early Abs, as well as recently identified broadly neutralizing Abs (bNAbs) targeting different envelope glycoprotein (Env) epitopes, to block HIV-1 transmission by immature and mature DCs to HIV-1–sensitive cells. Three bNAbs directed against the gp41 membrane proximal region of Env (2F5, 4E10, and 10E8) and three gp120 bNAbs targeting the CD4 binding site (b12, VRC01, and NIH45-46) were examined. In addition, eight glycan-dependent bNAbs targeting the V1V2 apex (PG9, PG16, and PGT145), the V3 loop (2G12, PGT121, and PGT128), and the gp120–gp41 interface of Env (PGT151 and 35O22) were tested. bNAbs that bound specific glycans showed, depending on the immature or mature state of the DC, diverse efficiencies in HIV-1 trans-infection. All bNAbs that bound the CD4 binding site blocked trans-infection, whereas all bNAbs directed against the membrane proximal region lost neutralizing activity after DC-mediated HIV-1 transmission. To understand how preneutralized HIV-1 can be transferred as infectious virus by DCs, we followed the processing of 2F5-treated HIV-1 by DCs with confocal microscopy. Inhibition of DC-internalization pathways could not reverse the dissociation of 2F5 from HIV-1, suggesting that Ab dissociation occurs directly at the plasma membrane. Collectively, these findings imply that the location of the epitope and the neutralization capacity of these Abs determine the efficiency of DC-mediated HIV-1 transfer.

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Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti–HIV-1 IgG without induction of maturation

Cited by 56 publications

References 63 publications

Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4⁺T Lymphocytes intrans

Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

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Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti–HIV-1 IgG without induction of maturation

Cited by 56 publications

References 63 publications

Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4+T Lymphocytes intrans

Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

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Dendritic Cells Preferentially Transfer CXCR4-Using Human Immunodeficiency Virus Type 1 Variants to CD4⁺T Lymphocytes intrans