Biomedical subjects

H Golding

Publications and source records attributed to H Golding.

At least 19 recordsLinked to original sources

PubMed1999

Increased association of glycoprotein 120-CD4 with HIV type 1 coreceptors in the presence of complex-enhanced anti-CD4 monoclonal antibodies.

CD4-specific monoclonal antibodies (CG1, CG7, and CG8), which bind with a 5- to 10-fold higher avidity to preformed CD4-gp120 complexes than to CD4, were previously shown to recognize newly identified conformational epitopes in the D1-CDR3 region of CD4. In the current study, these and other complex-enhanced MAbs were tested in three separate assays of HIV-1 coreceptor (CXCR4/CCR5) recruitment. In these assays, the CD4-specific MAbs CG1, -7, and -8 stabilized the association of coreceptor, gp120, and CD4 in trimolecular complexes. In contrast, the gp120-specific, complex-enhanced MAbs 48d and 17b were inhibitory. These data suggest that conformational changes in the CDR3 region of CD4-D1, induced by gp120 binding, may be involved in coreceptor association and thus play a positive role in the HIV-1 cell fusion process.

Antibodies, Monoclonal↗

PubMed1999

Fusion of monocytes and macrophages with HIV-1 correlates with biochemical properties of CXCR4 and CCR5.

Human macrophages can be infected more efficiently by M-tropic than by T-tropic HIV-1 strains, despite surface expression of both CXCR4 and CCR5 co-receptors. Western blot analyses of total cell extracts and surface proteins from multiple sets of monocytes and macrophages demonstrated substantial differences between CXCR4 molecules. CXCR4 was mainly a monomer in monocytes, but was mainly a species of higher molecular weight (90 kDa) on the surface of macrophages. CCR5 was monomeric in both cell types. A constitutive association between CD4 and the co-receptors was seen in monocytes and macrophages. However, CD4 co-precipitated with CCR5 and CXCR4 monomers, but not with the high-molecular-weight forms of CXCR4, indicating that the high-molecular-weight CXCR4 species in macrophages are not available for association with CD4, which may contribute to the inefficient entry of T-tropic strains into mature macrophages.

Animals↗

PubMed1999

Human herpesvirus 6 infects dendritic cells and suppresses human immunodeficiency virus type 1 replication in coinfected cultures.

Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progressive loss of CD4(+) T cells observed in AIDS patients. Because dendritic cells (DC) play an important role in the immunopathogenesis of human immunodeficiency virus (HIV) disease, we studied the infection of DC by HHV-6 and coinfection of DC by HHV-6 and HIV. Purified immature DC (derived from adherent peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody staining, and presence of virus in culture supernatants. However, HHV-6-infected DC demonstrated neither cytopathic changes nor functional defects. Interestingly, HHV-6 markedly suppressed HIV replication and syncytium formation in coinfected DC cultures. This HHV-6-mediated anti-HIV effect was DC specific, occurred when HHV-6 was added either before or after HIV, and was not due to decreased surface expression or function of CD4, CXCR4, or CCR5. Conversely, HIV had no demonstrable effect on HHV-6 replication. These findings suggest that HHV-6 may protect DC from HIV-induced cytopathicity in AIDS patients. We also demonstrate that interactions between HIV and herpesviruses are complex and that the observable outcome of dual infection is dependent on the target cell type.

Cell Survival↗

PubMed1998

Cytokines regulate expression and function of the HIV coreceptor CXCR4 on human mature dendritic cells.

HIV-infected dendritic cells (DC) efficiently transmit infection to CD4+ T cells during the process of T cell activation. To further understand interactions between DC and HIV, cytokine regulation of HIV coreceptors on cultured Langerhans cells (cLC, as prototypes of mature DC) was studied. Expression of cell surface CXCR4 on cLC was up-regulated by IL-4 and TGF-beta1 and inhibited by IFN-alpha, IFN-beta, and IFN-gamma, whereas cytokines did not appreciably regulate CCR5. Changes in cell surface CXCR4 expression on cLC correlated with T cell-tropic (X4)-HIV envelope-mediated syncytium formation and X4-HIV infection levels. A relative increase in the ratio of type 2/type 1 cytokine production, which can occur in HIV disease, may up-regulate CXCR4 expression on mature DC and promote infection by X4 viruses. Importantly, these findings suggest that cytokine dysregulation may be linked to the emergence of X4-HIV strains as HIV-infected individuals progress to AIDS.

CD4 Antigens↗

PubMed1998

HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in immunodeficient mice.

Enhancement of immunity in the setting of HIV infection is difficult owing to loss of functional CD4+ T cells. The MHC class II-deficient mouse (II-/-) environment simulates that of the immunocompromised HIV-infected individual, since these mice have low CD4+ T cell numbers, defective CD4-dependent responses, and are susceptible to opportunistic infection. This strain was used to test whether heat-killed Brucella abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses. V3-BA, but not the T-dependent antigen V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA in both wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-treated, but not V3-KLH-treated, II-/- mice developed serum IgG and IgA anti-V3 antibodies, with IgG2b and IgG3 as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, demonstrated that the antibodies generated by V3-BA in II-/- mice were capable of neutralizing HIV. These experiments demonstrate that a heat-inactivated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing antiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HIV-1 patients.

AIDS Vaccines↗

PubMed1998

CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection.

Thymocyte infection with HIV-1 is associated with thymic involution and impaired thymopoiesis, particularly in pediatric patients. To define mechanisms of thymocyte infection, we examined human thymocytes for expression and function of CXCR4 and CCR5, the major cell entry coreceptors for T cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) strains of HIV-1, respectively. CXCR4 was detected on the surface of all thymocytes. CXCR4 expression on mature, high level TCR thymocytes was similar to that on peripheral blood T cells, but was much lower than that on immature thymocytes, including CD34+ thymic progenitors. Consistent with this, stroma-derived factor-1 (SDF-1) induced calcium flux primarily in immature thymocytes, with CD34+ progenitors giving the strongest response. In addition, SDF-1 mRNA was detected in thymic-derived stromal cells, and SDF-1 induced chemotaxis of thymocytes, suggesting that CXCR4 may play a role in thymocyte migration. Infection of immature thymocytes by the T-tropic HIV-1 strain LAI was 10-fold more efficient than that in mature thymocytes, consistent with their relative CXCR4 surface expression. Anti-CXCR4 antiserum or SDF-1 blocked fusion of thymocytes with cells expressing the LAI envelope. In contrast to CXCR4, CCR5 was detected at low levels on thymocytes, and CCR5 agonists did not induce calcium flux or chemotaxis in thymocytes. However, CD4+ mature thymocytes were productively infected with the CCR5-tropic strain Ba-L, and this infection was specifically inhibited with the CCR5 agonist, macrophage inflammatory protein-1beta. Our data provide strong evidence that CXCR4 and CCR5 function as coreceptors for HIV-1 infection of human thymocytes.

Antigens, CD34↗

PubMed1998

FDA "reform"?

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Budgets↗

PubMed1998

Induction of HIV-1 IIIb neutralizing antibodies in BALB/c mice by a chimaeric peptide consisting of a T-helper cell epitope of Semliki Forest virus and a B-cell epitope of HIV.

A colinearly synthesized peptide consisting of a H-2d restricted T-helper cell epitope of Semliki Forest virus (SFV) and triple repeats of sequence GPGRAF, derived from the V3 domain of HIV-1 strains, was used to immunize BALB/c (H-2d) mice. Pepscan analysis of sera from peptide-immunized mice revealed that the chimaeric peptide GREKFTIRPHYGKEIGPGRAFGPGRAFGPGRAF contains three distinct antibody-reactive sequences GREKFTIR, PHYGKEI and GPGRAF. The chimaeric peptide evoked HIV-1 IIIb neutralizing antibodies in serum as measured in vitro by reduction of syncytia formation and reduction of p24 production as well. So, the T-helper cell epitope of SFV provided help to a small linear neutralization epitope of HIV-1 strains. Interestingly, the T-helper cell epitope alone might induce antibodies cross-reactive with HIV-1 IIIb specific peptide GPGRAFVTIGK which shows some homology (residues underlined) with the antibody-reactive sequence GREKTIR of SFV.

Amino Acid Sequence↗

PubMed1998

Co-ligation of alpha4beta1 integrin and TCR rescues human thymocytes from steroid-induced apoptosis.

Maturation of thymocytes represents a sequence of events during which thymocytes expressing TCR with moderate avidity for self antigen/MHC are positively selected, whereas those with high or insufficient TCR avidity die. Glucocorticoids are produced intrathymically and can contribute to apoptosis of unselected thymocytes. Thymocytes differentiate in a close contact with epithelial cells, expressing vascular adhesion molecule-1 (VCAM-1) and secreting glucocorticoids, with bone marrow-derived macrophages, and with extracellular matrix containing fibronectin (FN) and collagen. Their contact with FN is mediated by alpha4beta1 and alpha5beta1 integrins. We examined the contribution of TCR and integrin signaling to the survival of thymocytes from dexamethasone (Dex)-induced apoptosis. We demonstrate that FN and VCAM-1 (both of which bind alpha4beta1 integrin), but not collagen, considerably augment TCR-mediated protection of thymocytes from Dex-induced apoptosis. This 'survival' signal is transduced through the alphabeta1, but not through the alpha5beta1 integrin. The observed protection from Dex-induced apoptosis correlated with an increase in bcl-2 protein levels. FN-alpha4beta1 and VCAM-1-alpha4beta1 engagement induced up-regulation bcl-2 protein, while alpha5beta1 binding to FN induced a negative signal that was blocked by anti-alpha5beta1 antibody. These data suggest that alpha4beta1 integrin may contribute to protection of thymocytes with moderate avidity TCR from glucocorticoid-induced death during intrathymic maturation.

Antibodies, Monoclonal↗

PubMed1997

Safety and immunogenicity of UBI HIV-1MN octameric V3 peptide vaccine administered by subcutaneous injection.

Twenty-four HIV-seronegative men, at high risk of HIV infection, were recruited into a phase I/II safety and immunogenicity trial of a prototype HIV vaccine. The immunogen was a synthetic, monovalent, octameric HIV-1MN V3 peptide in an aluminum hydroxide (alum) adjuvant. The vaccine had been evaluated previously using a standard 0-, 1-, 6-month intramuscular schedule and was found to stimulate neutralizing antibody in 60-90% of volunteers. Participants were randomized to receive either 500 micrograms (n = 10; high dose) or 100 micrograms (n = 10; low dose) of immunogen or placebo (alum alone; n = 4) at 0, 1, and 6 months by subcutaneous injection. Responses to the immunogen were evaluated by enzyme-linked immunosorbent assay (ELISA)-detectable antibody and by proliferative responses. Safety was monitored by both clinical assessment and regular review with a clinical psychologist. No serious adverse experiences were observed following administration of the assigned medication. One individual (placebo) seroconverted while on study, following exposure to HIV. After the vaccination course only four individuals (three high dose and one low dose) had ELISA-detectable antibody against the immunogen. In the evaluable samples, from 19 volunteers, only 7 vaccine recipients (3 high dose and 4 low dose) had demonstrable lymphoproliferative responses to preparations of the immunogen. Subcutaneous administration of its candidate vaccine was safe but did not result in uniform or robust immunological responses.

AIDS Vaccines↗

PubMed1997

Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: implications for HIV primary infection.

Transmission of HIV-1 is predominantly restricted to macrophage (Mphi)-tropic strains. Langerhans cells (LCs) in mucosal epithelium, as well as macrophages located in the submucosal tissues, may be initial targets for HIV-1. This study was designed to determine whether restricted transmission of HIV-1 correlates with expression and function of HIV-1 co-receptors on LCs and macrophages. Using polyclonal rabbit IgGs specific for the HIV co-receptors cytokines CXCR4 and CCR5, we found that freshly isolated epidermal LCs (resembling resident mucosal LCs) expressed CCR5, but not CXCR, on their surfaces. In concordance with surface expression, fresh LCs fused with Mphi-tropic but not with T-tropic HIV-1 envelopes. However, fresh LCs did contain intracellular CXCR4 protein that was transported to the surface during in vitro culture. Macrophages expressed high levels of both co-receptors on their surfaces, but only CCR5 was functional in a fusion assay. These data provide several possible explanations for the selective transmission of Mphi-tropic HIV variants and for the resistance to infection conferred by the CCR5 deletion.

Amino Acid Sequence↗

PubMed1997

Enhancement of human immunodeficiency virus type 1 envelope-mediated fusion by a CD4-gp120 complex-specific monoclonal antibody.

The entry of human immunodeficiency virus type 1 (HIV-1) into cells is initiated by binding of the viral glycoprotein gp120-gp41 to its cellular receptor CD4. The gp120-CD4 complex formed at the cell surface undergoes conformational changes that may allow its association with an additional membrane component(s) and the eventual formation of the fusion complex. These conformational rearrangements are accompanied by immunological changes manifested by altered reactivity with monoclonal antibodies specific for the individual components and presentation of new epitopes unique to the postbinding complex. In order to analyze the structure and function of the gp120-CD4 complex, monoclonal antibodies were generated from splenocytes of BALB/c mice immunized with soluble CD4-gp120 (IIIB) molecules (J. M. Gershoni, G. Denisova, D. Raviv, N. I. Smorodinsky, and D. Buyaner, FASEB J. 7:1185-1187 1993). One of those monoclonal antibodies, CG10, was found to be strictly complex specific. Here we demonstrate that this monoclonal antibody can significantly enhance the fusion of CD4+ cells with effector cells expressing multiple HIV-1 envelopes. Both T-cell-line-tropic and macrophage-tropic envelope-mediated cell fusion were enhanced, albeit at different optimal doses. Furthermore, infection of HeLa CD4+ (MAGI) cells by HIV-1 LAI, ELI1, and ELI2 strains was increased two- to fourfold in the presence of CG10 monoclonal antibodies, suggesting an effect on viral entry. These findings indicate the existence of a novel, conserved CD4-gp120 intermediate structure that plays an important role in HIV-1 cell fusion.

Animals↗

PubMed1997

Human immunodeficiency virus type 1 infection of mature CD3hiCD8+ thymocytes.

Although CD4+ cells are the primary targets of human immunodeficiency virus type 1 (HIV-1) infection, earlier reports have suggested that intrathymic infection of CD8+ cells may occur. However, it was unclear whether HIV-1-infected CD8+ thymocytes were truly mature single-positive (SP) cells. In the present study, SCID mice implanted with human fetal thymus and liver tissues (SCID-hu mice) were infected with three primary isolates of HIV-1 and infected thymocytes were analyzed to assess maturational status. After intra-implant or intraperitoneal injection with HIV-1, thymocytes were sorted by three-color flow cytometric analysis into mature populations of CD3hiCD4+ and CD3hiCD8+ SP cells of > 99% purity (< 0.3% CD4-containing cells in the CD8+ population). The presence of HIV-1 provirus in the sorted thymocyte populations was determined by quantitative PCR. A fraction of mature CD3hiCD8+ thymocytes contained HIV-1 proviral DNA, and evidence of viral mRNA transcription in these cells was demonstrated by in situ hybridization. In contrast, when uninfected CD3hiCD8+ thymocytes were cocultured with HIV-1-infected CD4+ thymocytes, no evidence of productive HIV-1 infection was detected. Thus, HIV-1 infection of CD8+ thymocytes in the SCID-hu mouse does not occur by direct contact with the virus. Rather, cell surface CD4 is required; therefore, precursor cells are the likely primary target of HIV-1 infection in the thymus. During ontogeny, some of these infected cells continue their differentiation into mature CD8+ SP thymocytes that contain proviral DNA and express viral RNA.

Animals↗

PubMed1996

Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines.

Accessory cell-surface molecules involved in the entry of human immunodeficiency virus-type 1 into cells have recently been identified and shown to belong to the family of chemokine receptors. Treatment of human cell lines with soluble monomeric gp120 at 37 degrees C induced an association between the surface CD4-gp120 complex and a 45-kilodalton protein, which can be down-modulated by the phorbol ester phorbol 12-myristate 13-acetate. The three proteins were coprecipitated from the cell membranes with antibodies to CD4 or to gp120. The 45-kilodalton protein comigrated with fusin on sodium dodecyl sulfate gels and reacted with rabbit antisera to fusin in protein immunoblots. No 45-kilodalton protein could be coprecipitated from similarly treated nonhuman cells. However, infection of 3T3.CD4.401 cells with vaccinia-fusin recombinant virus (vCBYF1), followed by gp120 treatment, resulted in coprecipitation of fusin and CD4.401 molecules from their membranes. Together these data provide evidence for physical association between fusin and the CD4-gp120 complex on cell membranes.

3T3 Cells↗

PubMed1996

Brucella abortus as a potential vaccine candidate: induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion molecule 1 surface expression in elutriated human monocytes stimulated by heat-inactivated B. abortus.

Development of a vaccine which is capable of generating a strong cellular immune response associated with gamma interferon (IFN-gamma) production and cytotoxic T-cell development requires that the immunogen be capable of inducing the secretion of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram-negative bacterium Brucella abortus can induce IFN-gamma secretion by T cells. In the present study, we demonstrate that B. abortus and lipopolysaccharide (LPS) from B. abortus can induce IL-12 p40 mRNA expression and protein secretion by human elutriated monocytes (99% pure). p40 mRNA was detected within 4 h, and p40 protein could be measured at 24 h. This induction was abrogated by anti-CD14 monoclonal antibody, suggesting that monocytes recognize B. abortus via their receptor for LPS. The biological activity of IL-12 secreted by B. abortus-stimulated monocytes was demonstrated by its ability to upregulate IFN-gamma mRNA expression in T cells separated from monocytes and B. abortus by a transwell membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity against K562 target cells. B. abortus was shown to rapidly increase the expression of the costimulatory molecules B7.1 and B7.2 and intercellular adhesion molecule 1 on human monocytes. Together, these data indicate that B. abortus can directly activate human monocytes and provide the cytokine milieu which would direct the immune response towards Th1-Tc1 differentiation.

Antigens, CD↗

PubMed1996

Brucella abortus conjugated with a peptide derived from the V3 loop of human immunodeficiency virus (HIV) type 1 induces HIV-specific cytotoxic T-cell responses in normal and in CD4+ cell-depleted BALB/c mice.

We have previously shown that immunization of mice with human immunodeficiency virus (HIV)-derived proteins or peptides conjugated to inactivated Brucella abortus induces the secretion of virus-neutralizing antibodies, predominantly of the immunoglobulin G2a (IgG2a) isotype. In addition, B. abortus activates human CD4+ and CD8+ cells to secrete gamma interferon. Since these are both characteristics of a Th1-type immune response, which is associated with the development of cell-mediated immunity, it was important to determine if B. abortus conjugates would also act as a carrier to induce a cytotoxic T-lymphocyte (CTL) response. To test this hypothesis, we conjugated an 18-amino-acid peptide from the V3 loop of the MN strain of HIV-1 gp120 that contains both B- and cytotoxic T-cell epitopes to B. abortus (B. abortus-MN 18-mer). A 10-amino-acid fragment of this peptide has been shown to be the minimal CTL determinant presented by murine H-2Dd. It was found that two in vivo immunizations with 10(8) organisms of B. abortus-MN 18-mer followed by in vitro stimulation with peptide induced a virus-specific CTL response. Conjugation to B. abortus was required for in vivo priming, since there was no induction of memory CTLs when B. abortus was only mixed with peptide. Targets pulsed with peptide as well as those infected with a vaccinia virus encoding HIV gp160 were killed, demonstrating recognition of naturally processed envelope. Also, major histocompatibility complex-incompatible L cells which were infected with vaccinia viruses that encoded H-2Dd, but not H-2Kd, and pulsed with peptide were lysed. This demonstrated the appropriate major histocompatibility complex class I restriction. Treatment of the mice with anti-L3T4 prior to immunization caused a severe depletion of CD4+ lymphocytes, yet it did not decrease the CTL priming. Thus, inactivated B. abortus can induce non-CD4+ cells to produce the cytokines required for CTL induction. We conclude that B. abortus stimulates a cellular as well as a humoral immune response, even in the relative absence of CD4+ helper cells. It may be a particularly useful vaccine carrier in HIV-1-infected individuals or others with impaired CD4+ T-cell function.

AIDS Vaccines↗

PubMed1995

Human peripheral blood CD4+ and CD8+ T cells express Th1-like cytokine mRNA and proteins following in vitro stimulation with heat-inactivated Brucella abortus.

Defining the pattern of lymphokine production associated with Brucella abortus is critical for advancing the development of B. abortus as a vaccine carrier. In the present study we investigated the ability of heat-inactivated B. abortus or lipopolysaccharide from B. abortus to induce lymphokine production from purified human T cells in vitro. Gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 induction was assayed by mRNA-specific PCR and by enzyme-linked immunosorbent assay and bioassay for protein production. Following depletion of monocytes and B cells, B. abortus increased IFN-gamma and IL-2 mRNA expression in purified T cells compared with expression in unstimulated cells. In contrast, no IL-5 mRNA expression and only transient low-level IL-4 mRNA expression and no IL-4 protein secretion were detected. Phytohemagglutinin or phorbol myristate acetate plus ionomycin induced mRNA and protein for all these cytokines. Similar results were obtained with LPS purified from B. abortus. Removal of NK cells did not reduce lymphokine production, and enriched NK cells did not express IFN-gamma mRNA or secrete IFN-gamma protein in response to B. abortus, indicating that NK cells were not the responding population. Both CD4+ and CD8+ populations produced IFN-gamma and IL-2 in response to B. abortus. Preincubation of resting T cells with B. abortus or LPS from B. abortus for 7 days induced their differentiation into Th1-like cells as judged by their subsequent lymphokine response to phorbol myristate acetate plus ionomycin. These results suggest that B. abortus can induce differentiation of Th0 into Th1-type cells.

Base Sequence↗

PubMed1995

Phorbol ester-induced down modulation of tailless CD4 receptors requires prior binding of gp120 and suggests a role for accessory molecules.

The entry of human immunodeficiency virus type 1 into cells proceeds via a fusion mechanism that is initiated by binding of the viral glycoprotein gp120-gp41 to its cellular receptor CD4. Species- and tissue-specific restrictions to viral entry suggested the participation of additional membrane components in the postbinding fusion events. In a previous study (H. Golding, J. Manischewitz, L. Vujcic, R. Blumenthal, and D. Dimitrov, J. Virol. 68:1962-1968, 1994), it was found that phorbol myristate acetate (PMA) inhibits human immunodeficiency virus type 1 envelope-mediated cell fusion by inducing down modulation of an accessory component(s) in the CD4-expressing cells. The fusion inhibition was seen in a variety of cells, including T-cell transfectants expressing engineered CD4 receptors (CD4.401 and CD4.CD8) which are not susceptible to down modulation by PMA treatment. In the current study, it was found that preincubation of A2.01.CD4.401 cells with soluble monomeric gp120 for 1 h at 37 degrees C primed them for PMA-induced down modulation (up to 70%) of the tailless CD4 receptors. The gp120-priming effect was temperature dependent, and the down modulation may have occurred via clathrin-coated pits. Importantly, nonhuman cell lines expressing tailless CD4 molecules did not down modulate their CD4 receptors under the same conditions. The gp120-dependent PMA-induced down modulation of tailless CD4 receptors could be efficiently blocked by the human monoclonal antibodies 48D and 17B, which bind with increased avidity to gp120 that was previously bound to CD4 (M. Thali, J. P. Moore, C. Furman, M. Charles, D. D. Ho, J. Robinson, and J. Sodroski, J. Virol. 67:3978-3988, 1993). These findings suggest that gp120 binding to cellular CD4 receptors induces conformational changes leading to association of the gp120-CD4 complexes with accessory transmembrane molecules that are susceptible to PMA-induced down modulation and can target the virions to clathrin-coated pits.

Animals↗