Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro

Robinson, William E.; Gorny, M. K.; Xu, Jian-Yin; Mitchell, William M.; Zolla‐Pazner, Susan

doi:10.1128/jvi.65.8.4169-4176.1991

Cited by 119 publications

(48 citation statements)

References 40 publications

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“…The ability of gp41 viral envelope antigen lo bloek C'-ADE in our system concurs with the results presented by Robinson et ai [33]. Their data show that antibodies mediating C'ADE of HIV-1 infection in MT-2 cells are reactive wilh two immunodominanl epitopes of HIV-1 iransmembrane glycoprotein gp4L In contrast lo C'-ADE.…”

Section: Discussionsupporting

confidence: 92%

Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells culturedin vitro

Tóth

Mosborg-Petersen

Kiss

et al. 1994

Clinical and Experimental Immunology

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SUMMARY We examined if Fc receptor‐mediated antibody‐dependent enhancement (FcR‐ADE) or complement‐mediated antibody‐dependent enhancement (C′‐ADE) of virus infection can contribute to increasing replication of HIV‐1 in human syncytiotrophoblast (ST) cells. Here we report that both FcR‐ADE and C′‐ADE may result in enhanced virus release from HIV‐1‐infected ST cells. We show that FcR‐ADF of HIV‐1 infection in ST cells is mediated by FcRIII and other FcR(s) belonging to undetermined Fc classes and does not require CD4 receptors, whereas C'‐ADE uses both CD4 and CR2‐like receptors. FcR‐ADE: seems to be more efficient in enhancing HIV‐I replication than C′‐ADE. While FcR‐ADE leads to increased internalization of HIV‐1. C′‐ADE does not result in enhanced endocytosis of the virus. In addition, antibodies mediating FcR‐ADE arc reactive with the gp120 viral envelope antigen, whereas antibodies involved in C′‐ADE react with the viral transmembrane glycoprotein gp41. Data suggest that both FcR‐ADH and C′‐ADE may contribute lo the spread of HIV‐1 from mother to the fetus.

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Section: Discussionsupporting

confidence: 92%

Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells culturedin vitro

Tóth

Mosborg-Petersen

Kiss

et al. 1994

Clinical and Experimental Immunology

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“…An antibody to FL2 provides further insight into the way FR1 functions. In a variety of viruses, antibodies raised to fusion peptides and loops have neutralizing properties, and the prevailing thought is that these loops and peptides are hidden until the fusion protein goes from a pre-to a postfusion state (54)(55)(56)(57)(58)(59). Yet an antibody against an FL2 peptide was neutralizing for both HSV-1 (data not shown) and HSV-2, implying that some portion of the FLs or the surrounding residues are exposed on full-length gB when it is in the viral membrane.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Neutralization of Herpes Simplex Virus by Antibodies Directed at the Fusion Domain of Glycoprotein B

Cairns

Fontana

Huang

et al. 2014

J Virol

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Glycoprotein B (gB), the fusogen of herpes simplex virus (HSV), is a class III fusion protein with a trimeric ectodomain of known structure for the postfusion state. Seen by negative-staining electron microscopy, it presents as a rod with three lobes (base, middle, and crown). gB has four functional regions (FR), defined by the physical location of epitopes recognized by anti-gB neutralizing monoclonal antibodies (MAbs). Located in the base, FR1 contains two internal fusion loops (FLs) and is the site of gB-lipid interaction (the fusion domain). Many of the MAbs to FR1 are neutralizing, block cell-cell fusion, and prevent the association of gB with lipid, suggesting that these MAbs affect FL function. Here we characterize FR1 epitopes by using electron microscopy to visualize purified Fab-gB ectodomain complexes, thus confirming the locations of several epitopes and localizing those of MAbs DL16 and SS63. We also generated MAb-resistant viruses in order to localize the SS55 epitope precisely. Because none of the epitopes of our anti-FR1 MAbs mapped to the FLs, we hyperimmunized rabbits with FL1 or FL2 peptides to generate polyclonal antibodies (PAbs). While the anti-FL1 PAb failed to bind gB, the anti-FL2 PAb had neutralizing activity, implying that the FLs become exposed during virus entry. Unexpectedly, the anti-FL2 PAb (and the anti-FR1 MAbs) bound to liposome-associated gB, suggesting that their epitopes are accessible even when the FLs engage lipid. These studies provide possible mechanisms of action for HSV neutralization and insight into how gB FR1 contributes to viral fusion. IMPORTANCEFor herpesviruses, such as HSV, entry into a target cell involves transfer of the capsid-encased genome of the virus to the target cell after fusion of the lipid envelope of the virus with a lipid membrane of the host. Virus-encoded glycoproteins in the envelope are responsible for fusion. Antibodies to these glycoproteins are important biological tools, providing a way of examining how fusion works. Here we used electron microscopy and other techniques to study a panel of anti-gB antibodies. Some, with virusneutralizing activity, impair gB-lipid association. We also generated a peptide antibody against one of the gB fusion loops; its properties provide insight into the way the fusion loops function as gB transits from its prefusion form to an active fusogen. Herpes simplex virus (HSV) has four envelope glycoproteins that are essential for virus entry into cells: glycoproteins gD, gH, gL, and gB. All herpesviruses use a combination of gB and the heterodimer gH/gL to carry out virus-cell fusion, with current evidence indicating that gB is the fusion protein (1-4). Like most alphaherpesviruses, HSV also requires the receptor-binding protein gD to carry out fusion. Our current model of HSV fusion starts with the binding of gD to one of its receptors (nectin-1, herpesvirus entry mediator [HVEM], or 3-O-sulfotransferase [3-OST] heparan sulfate) (5), transmitting a physical signal to gH/gL, which, in turn, acts upon gB t...

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“…An associated fact is that individual epitopes are capable of mediating both virus neutralization (VN) and ADE of virus infectivity. This has been clearly shown for DV (Halstead, et al, 1984;Morens and Halstead, 1990) and HIV (Robinson, et al, 1991 ), as well as for FIPV Hohdatsu, et al, 1991 a;Olsen, et al, 1992b). Does the subclass of a given Ab determine whether it is able to mediate both neutralization and ADE of virus infectivity?…”

Section: Antibody-dependent Enhancement Of Virus Infectivitymentioning

confidence: 94%

A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination

Olsen

1993

Veterinary Microbiology

112

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Feline infectious peritonitis (FIP) has been an elusive and frustrating problem for veterinary practitioners and cat breeders for many years. Over the last several years, reports have begun to elucidate aspects of the molecular biology of the causal virus (FIPV). These papers complement a rapidly growing base of knowledge concerning the molecular organization and replication of coronaviruses in general. The fascinating immunopathogenesis of FIPV infection and the virus' interaction with macrophages has also been the subject of several recent papers. It is now clear that FIPV may be of interest to scientists other than veterinary virologists since its pathogenesis may provide a useful model system for other viruses whose infectivity is enhanced in the presence of virus-specific antibody. With these advances and the recent release of the first commercially-available FIPV vaccine, it is appropriate to review what is known about the organization and replication of coronaviruses and the pathogenesis of FIPV infection.

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Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro

Cited by 119 publications

References 40 publications

Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells culturedin vitro

Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells culturedin vitro

Mechanism of Neutralization of Herpes Simplex Virus by Antibodies Directed at the Fusion Domain of Glycoprotein B

A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination

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