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J V Torres

Publications and source records attributed to J V Torres.

At least 37 records · Page 2Linked to original sources
PubMed1999

Simian retrovirus receptor and neutralization mechanism by antibodies to the envelope glycoprotein.

Type D simian retroviruses (SRV) cause an acquired immunodeficiency syndrome (AIDS) in monkeys. Results of infection with SRV range from complete recovery with absence of viremia to a viremic state, which produces AIDS-like symptoms and culminates in death. These varied outcomes render the interaction of the host and SRV an attractive model for the study of immunosuppressive retrovirus resulting in different pathologic consequences. We describe here the isolation and determination of the molecular weight of the receptor for SRV. We demonstrate that a cell receptor with the same molecular weight is bound by the envelope protein of all five serotypes of SRV. We also show that the receptor recognizes a region containing amino acids 142-167 of the envelope protein of SRV serotype 1 (SRV-1). In addition, we show that a different region of SRV serotype 2 (SRV-2) envelope protein containing amino acids 93-106, interacts with a cell receptor of identical molecular weight. Furthermore, polyclonal and monoclonal antibodies that are directed to envelope epitopes 142-167 of SRV-1 or to 93-106 of SRV-2, specifically neutralize only the respective viral serotype. Our results indicate that the neutralization of SRV infectivity by antibodies is achieved through blocking the interaction between the virus and its cell receptor.

Antibodies, Viral↗
PubMed1999

Nuclear magnetic resonance analysis of solution conformations in C4-V3 hybrid peptides derived from human immunodeficiency virus (HIV) type 1 gp120: relation to specificity of peptide-induced anti-HIV neutralizing antibodies.

Immunogenic peptides containing epitopes of the gp120 C4 and V3 regions from human immunodeficiency virus strains MN and EV91 have been studied by nuclear magnetic resonance and molecular modeling and used as immunogens in rhesus monkeys. The results, combined with those for other peptides, suggest a correlation between solution conformation and immunologic cross-reactivity.

Amino Acid Sequence↗
PubMed1998

Hypervariable epitope constructs representing variability in envelope glycoprotein of SIV induce a broad humoral immune response in rabbits and rhesus macaques.

Using synthetic peptides, we developed an approach to account for protein epitope variability. We have prepared, in a single synthesis, a cocktail of peptides we have designated a hypervariable epitope construct (HEC), which collectively represents much of the in vivo variability seen in an epitope. Eight HECs representing the in vivo variability seen throughout the envelope glycoprotein of the simian immunodeficiency virus (SIV) were designed and synthesized. The constructs were collectively conjugated to KLH (HEC-KLH) or recombinant gp130 (HEC-rgp130) and used to immunize rabbits and rhesus macaques, respectively. Using sera collected from rabbits immunized with HEC-KLH, we demonstrated that individual components of the immunogen were recognized as antigen in ELISAs, and that the induced antibodies cross-reacted with several strains of SIV as well as with a strain of HIV-2. Following immunization of macaques with HEC-rgp130 antiviral antibodies were induced. These antibodies were still present 9.5 months after the last boost and were also capable of recognizing several different strains of SIV, including SIVmac239, SIVmac251, and SIVsmH3, as well as a strain of HIV-2 (HIV-2ROD). In addition, the antibodies were also capable of neutralizing SIV viral infectivity in vitro. Peripheral blood lymphocytes (PBLs) from immunized macaques proliferated in response to whole proteins and virus. Finally, sera from monkeys immunized with SIV, rgp130, and HIV-2 as well as sera from HIV-2-positive humans recognized HECs in ELISAs, demonstrating the relevance of these epitopes in vivo. This approach can be used as an effective method for generating a strong, broadly cross-reactive humoral response against HIV and can serve as an important component of combination vaccines against HIV and AIDS.

Amino Acid Sequence↗
PubMed1997

Identification of a synthetic peptide that mimics an HIV glycoprotein 120 envelope conformational determinant exposed following ligation of glycoprotein 120 by CD4.

CD4 ligation of HIV envelope gp120 results in conformational changes in gp120 that lead to exposure of the gp41 fusogenic domain and fusion with the host cell membrane. One determinant at or near the CD4-binding site exposed on gp120 subsequent to CD4 binding is defined by two human MAbs termed 17b and 48d. These MAbs do not block CD4 binding to gp120; rather, their binding to gp120 is upregulated following CD4 binding. To determine if synthetic peptide mimetopes could be found that reflect conformational determinants on the surface of gp120, synthetic gp120 peptides from 10 divergent HIV isolates were screened for their ability to bind to 17b and 48d in ELISAs. Although MAb 48d binds to HIV IIIB recombinant gp120 protein, in our studies 48d selectively bound only to the HIV Can0A V3 peptide and not to HIV IIIB V3 peptide, whereas MAb 17b bound none of the peptides tested. Monoclonal antibody 48d bound to the HIV Can0A V3 peptide both in solid-phase ELISA and in solution in a competitive ELISA, but could not bind to HIV Can0A V3 peptide bound to human T cells. The HIV Can0A V3 peptide induced anti-HIV antibodies in rhesus monkeys that neutralized the laboratory-adapted HIV MN strain but did not induce antibodies that neutralized HIV IIIB/LAI, HIV SF-2, or HIV RF isolates, or that neutralized HIV primary isolates. These data suggested that the primary sequence of the HIV Can0A V3 loop exists in a conformer that mimicks a non-V3 determinant of native gp120 exposed subsequent to CD4 binding on the surface of gp120 of laboratory-adapted HIV strains. Structural studies of the Can0A V3 peptide and/or the 48d MAb may provide important information regarding the nature of gp120 conformational changes that occur following gp120 ligation by CD4.

Amino Acid Sequence↗
PubMed1997

Cytogenetic findings in malignant mixed mesodermal tumors of the uterus.

Cytogenetic analyses of four malignant mixed mesodermal tumors (MMMT) of the uterus are reported, of which one was of the homologous type and three of the heterologous. Karyotypic analyses were obtained in two cases from original tumors and in two cases from tumors xenotransplanted into nude mice. The karyotype of the homologous MMMT was normal in three different passages of a nude mice xenograft line established from the primary tumor. The heterologous tumors showed normal karyotype in one case and hyperdiploid and near triploid range with extensive numerical and structural rearrangements in two cases. Deletion of chromosome 1 at p32, and deletion of chromosome 11 at q13 were common markers in anomalous cases. The chromosomes most often involved in structural rearrangements were chromosomes 1, 9, 11, 12, 17, and 19. Double minutes, homogeneously staining regions, and telomeric association were also seen.

Aged↗
PubMed1995

Properties of virus-like particles produced by SIV-chronically infected human cell clones.

SIVsm chronically infected cultures were obtained after infection of CEMX174 cells with either SIVsmH3 or SIVsmE660. These phenotypically CD4 cells, formed syncytia but only when cocultivated with CD4+ cells. Single cell clones were derived from these cultures and examined for the production of virus-specific proteins. The majority of the clones expressed SIV p27 antigen and low levels of virus reverse transcriptase activity. Western blot analysis, performed with either monoclonal or polyclonal sera, showed that a chronically infected clone (B7) produced particles which contained envelope (gp135 and gp43), gag precursors and gag proteins (p27, p16 and p8). However, these particles (SIVsmB7) lacked detectable levels of vpx and of integrase, and contained several fusion proteins which expressed viral protease antigens. This defective virus failed to infect established CD4+ cell lines, as well as primary cultures of macrophages and of peripheral blood lymphocytes, obtained both from humans and from rhesus macaques. Lack of infection correlated with lack of viral DNA detection by PCR amplification of genomic DNA extracted from these cell cultures. In addition, SIVsmB7 virus lacked infectivity in vivo. Rhesus macaques inoculated with high concentrations of SIVsmB7 showed no viremia and their PBMC were PCR negative. Thus, B7 cells produced stable, non-infectious virus mutants, which contained env and gag proteins, but lacked detectable amounts of vpx and of enzymes required for virus replication. Due to the high constitutive expression of this virus-like particle, we are now testing this preparation as a vaccine.

Animals↗
PubMed1994

Hypervariable epitope constructs as a means of accounting for epitope variability.

Epitope variability is one of the greatest obstacles to development of synthetic peptide vaccines. Based on a recently described hypervariable epitope (aa 414-434) on the envelope glycoprotein (gp130) to simian immunodeficiency virus (SIVmac142), we have developed a novel approach to account for epitope variability. We have prepared, in a single synthesis, a cocktail of peptides, designated a hypervariable epitope construct (HEC), which collectively represent all the in vivo variability seen in an epitope. The HEC represents permutations of amino acid substitutions found in the epitope and has been able to induce antibodies with enhanced binding to native SIV and broad immunoreactivity to related epitope analogues.

Amino Acid Sequence↗
PubMed1994

Diagnosis of endometrial carcinoma: predictive value of transvaginal color Doppler.

The objective of this study was to determine whether transvaginal ultrasound plus color Doppler flow improve the ability to diagnose endometrial carcinoma and allow better discrimination between benign and malignant endometrial lesions. One hundred thirty women with abnormal uterine bleeding were evaluated with transvaginal color Doppler before fractional dilatation and curettage (D&C). The endometrial line thickness and endometrial characteristics were evaluated by endosonography. The resistive and pulsatile indices of the uterine arteries and of the endometrium were evaluated with transvaginal color Doppler. Following D&C and tissue diagnosis, women were divided into two groups, 62 with a histologic diagnosis of endometrial adenocarcinoma and 68 with benign endometrial tissue. All women with endometrial carcinoma underwent TAH and BSO. A complete histopathologic study was done an all surgical specimens. The International Federation of Gynecology and Obstetrics (FIGO) stage and tissue grading were determined in all cases. The histopathologic findings were correlated with ultrasound and transvaginal color Doppler results. Patients with adenocarcinoma had an average endometrial thickness of 26.13 mm (range 8-87 mm). The average thickness for functional endometrium (proliferative) was 10.5 mm (range 6-23 mm). There was no case of carcinoma where the endometrial thickness was less than 8 mm. Intraendometrial neovascularization was not observed in any case with functional or atrophic endometrium. The flow indices in patients with endometrial adenocarcinomas are significantly different from the flow indices of patients with benign endometrial tissue. Transvaginal color Doppler increases the sensitivity of endometrial malignancy diagnosis. The method is capable of detecting important differences in flow indices and endometrial line characteristics between benign and malignant endometrial tissue.

Adenocarcinoma↗
PubMed1994

Oligopeptide-based enzyme immunoassay for ovine lentivirus antibody detection.

Ovine progressive pneumonia virus (OPPV) is a lentivirus which causes a progressive disease in sheep. Immunodominant epitopes have been identified in the envelope gp40 glycoprotein. Synthetic peptides representing these regions are able to detect the presence of OPPV antibodies in 96% of infected sheep.

Amino Acid Sequence↗
PubMed1994

Opportunistic invasion of the heart in Hispanic patients with acquired immunodeficiency syndrome.

One hundred consecutive patients who died of the acquired immunodeficiency syndrome (AIDS) were studied with an emphasis on the heart. Thirty-two patients showed pathologic changes. The pathologic findings included infection by Histoplasma capsulatum, Toxoplasma gondii, Mycobacterium tuberculosis, cytomegalovirus. Cryptococcus neoformans, and atypical mycobacteria. Noninfectious pathologic findings included nonspecific myocarditis, focal necrosis, focal fibrosis, and acute subendocardial infarction.

AIDS-Related Opportunistic Infections↗
PubMed1993

Induction of HIVMN neutralizing antibodies in primates using a prime-boost regimen of hybrid synthetic gp120 envelope peptides.

We have tested synthetic peptides composed of Th (T1) and V3 loop B cell neutralizing determinants [SP10 MN(A)] of HIVMN gp120 and the fusogenic (F) domain of gp41 as immunogens in rhesus monkeys. After two immunizations with either HIV env peptide T1-SP10 MN(A) or F-T1-SP10 MN(A), rhesus monkey serum neutralization titers against the HIVMN isolate ranged from 1:160 to 1:1400, and in cell-cell syncytium inhibition assay ranged from 1:20 to 1:80. However, in contrast to animals immunized with T1-SP10 MN(A), animals immunized twice with F-T1-SP10 MN(A) had no rise in anti-gp120 and neutralizing antibodies with an additional immunization with F-T1-SP10 MN(A) peptide. One of 4 rhesus monkeys (18987) had anti-HIVMN antibodies that cross-neutralized divergent HIV isolates HIVIIIB and HIVRF. Serum from animal 18987 neutralized 5 of 10 HIV isolates tested, and neutralizing activity against HIVIIIB of 18987 serum was absorbed with the conserved gp120 loop V3 sequence IGPGRAF. Anti-HIV neutralizing antibodies were boosted after a 6-mo rest by 500 micrograms of T1-SP10 MN(A) in 4 of 4 animals previously immunized with T1-SP10 MN(A) and in 2 of 2 animals previously immunized with F-T1-SP10 MN(A). However, immunization after 6-mo rest of animal 18987 with 500 micrograms of T1-SP10 MN(A) peptide, although boosting anti-HIVMN neutralizing antibodies, selectively did not boost cross-neutralizing anti-HIVIIIB antibodies. Thus, synthetic peptides containing T and B cell epitopes of HIV gp120 can induce high levels of anti-HIVMN neutralizing antibodies in primates.

Amino Acid Sequence↗
PubMed1993

An epitope on the surface envelope glycoprotein (gp130) of simian immunodeficiency virus (SIVmac) involved in viral neutralization and T cell activation.

SIVmac infection of macaques is an important animal model for HIV infection and AIDS; this model is being utilized for development of antiviral therapies and vaccines. In the present article, we sought to identify neutralization epitopes of SIVmac envelope surface glycoprotein (gp130). Algorithms were used to predict antigenicity of specific regions. Four regions from the primary amino acid sequence of the viral surface glycoprotein were selected. A synthetic peptide representing one of these regions (414-434) induced virus-neutralizing antibodies in mice; in addition, this peptide induced T cell-proliferative responses in macaques. To address the in vivo relevance of these observations, we demonstrated that experimentally infected macaques produce antibodies to the neutralization epitope. In addition, rhesus macaques protected against infection by an inactivated SIV vaccine develop antibodies that bind to peptide 414-434. These observations demonstrate that the region that includes the sequence 414-434 in the fourth variable domain (V4) of SIVmac gp130 contains both a linear neutralization epitope and a T cell epitope.

AIDS Vaccines↗
PubMed1991

Isolation and characterization of the neutralizable epitope of simian retrovirus-1 (SRV-1) and of the cell receptor for the virus.

An area encompassing residues 142-167 of the envelope protein of type D simian retrovirus (SRV-1) has been shown to contain the epitope to which neutralizing antibodies are directed. This area has been synthesized and shown to bind to monkey and mouse antiviral antibodies and to a virus neutralizing mouse monoclonal antibody. Protein conjugates of this peptide as well as the cross-linked or the free peptide induce antibodies capable of neutralizing, in vitro, viral infectivity. The cell receptor to the virus was isolated following extraction of Raji cells with non-ionic detergents. The receptor was isolated and characterized following radioimmuno-precipitation of 125I labeled cell extract bound to viral envelope protein. This immunoprecipitation could be inhibited by antiserum to peptide 142-167. Analysis in gels indicate that the receptor is of molecular weight of approximately 60 KDa. These results indicate that the neutralizing antibodies and the receptor recognize the same area on the viral envelope protein and that neutralization is the result of blocking the virus-receptor interaction by antibodies.

Amino Acid Sequence↗
PubMed1991

Immunobiological properties of a recombinant simian retrovirus-1 envelope protein and a neutralizing monoclonal antibody directed against it.

We previously reported that an area encompassing amino acids 147-162 of the envelope region of the simian (type D) retrovirus serotype 1 (SRV-1) constitutes an antigenic site for the binding of murine and rhesus neutralizing antibodies. Neutralizing antibodies to SRV-2 are directed to a different area, encompassing residues 96-102 of SRV-2. This paper presents data on the activity of an SRV-1 recombinant envelope protein (rEP) and of monoclonal hybridoma cell line, C11B8, produced from murine spleen cells immunized with SRV-1 rEP. Purified monoclonal antibodies from C11B8 bind to the SRV-1 rEP and to both SRV-1 and SRV-2. However, the monoclonal antibody exhibits strain specificity in the capacity to neutralize SRV-1 infection in vitro. Thus, C11B8 neutralizes SRV-1 infection but fails to neutralize four other known serotypes of the virus. C11B8 also binds to an SRV-1 synthetic peptide representing residues 142-167, which encompasses the previously defined antigenic site of recognition for neutralizing antibodies to SRV-1. This paper also contains evidence that the SRV-1 rEP construct binds the site for SRV-1 attachment to the cell receptor. This is indicated by the ability of SRV-1 rEP to compete with SRV-1 (but not with SRV-2) and inhibit its infectivity in vitro. In addition, SRV-1 rEP inhibits the neutralizing activity of C11B8 against SRV-1 infection in vitro. SRV-1 rEP has no inhibitory effect on rhesus neutralizing antibodies to SRV-2. Taken together, the above findings indicate that immunity conferred at the level of neutralizing antibodies during SRV infection is strain-specific and involves the recognition of envelope sequences unique to each strain.

Amino Acid Sequence↗
PubMed1991

The induction of neutralizing antibodies by synthetic peptides of the envelope protein of type D simian retrovirus-1 (SRV-1).

It has been recently demonstrated that two serotypes of type D simian retroviruses, namely SRV-1 and SRV-2, exhibit extensive immunological cross-reactivity but do not exhibit cross-reactivity at the level of neutralizing antibodies. We have also shown recently that an area which includes residues 147-162 of the envelope protein of SRV-1 constitutes an epitope to which neutralizing antibodies against SRV-1 but not against SRV-2 are directed. However, in spite of the capacity of various immunogenic preparations to induce antibodies which react with SRV-1 these antibodies were incapable of neutralizing in vitro viral infectivity. Work reported herein demonstrates that various immunogens consisting of a larger peptide, namely 142-167 of the envelope protein of SRV-1, induce antibodies capable of binding with the envelope protein of SRV-1 and with the whole virus. Moreover, these antibodies exhibit the capacity to neutralize in vitro the infectivity of SRV-1 but not of SRV-2.

Amino Acid Sequence↗
PubMed1991

Characterization of rhesus macaque B-lymphoblastoid cell lines infected with simian type D retrovirus.

A simian type D retrovirus designated SRV induces a fatal immunosuppressive disease in rhesus macaques. This syndrome shows many clinical similarities to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus-infected individuals. To investigate the mechanisms of immune dysfunction in SRV infection, we have focused on the interactions of SRV serotype 1 (SRV-1) with macaque B-lymphoblastoid cell lines (B-LCL). Procedures were optimized for establishing B-LCL by immortalization of macaque B lymphocytes with rhesus Epstein-Barr virus (EBV). These cell lines express B-cell surface markers, secrete immunoglobulins of the IgG or IgM isotypes, and release EBV which transforms monkey B cells. In vitro cultures of B-LCL supported replication of SRV-1. Several B-LCL infected with SRV-1 showed downregulation of major histocompatibility complex (MHC) class II antigen expression whereas levels of MHC class I antigen remained unchanged. Infection of B-LCL with SRV-1 did not alter the level of secreted immunoglobulin. Rhesus EBV was also used to obtain B-LCL from macaques infected with SRV-1; these cell lines were found to release infectious SRV-1. Investigations on the interactions of SRV-1 with B cells will be useful for elucidating mechanisms involved in the immunopathogenesis of primate retroviruses.

Animals↗