R C Gallo’s research while affiliated with University of Maryland, Baltimore and other places

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Publications (621)


Erratum: Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection (Proceedings of the National Academy of Sciences of the United States of America (2015) 112 (E992–E999) DOI: 10.1073/pnas.1423669112)
  • Article

May 2015

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13 Reads

Proceedings of the National Academy of Sciences

T.R. Fouts

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I.J. Prado

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[...]

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R.C. Gallo

The authors note that Fig. 3 appeared incorrectly. The corrected figure and its legend appear below. (Figure Presented).



112 Diversity of Specificity and Function Among Human Antibodies to Transitional Epitopes Altered by CD4 Binding to the HIV-1 Env Glycoprotein

April 2012

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4 Reads

JAIDS Journal of Acquired Immune Deficiency Syndromes

The HIV-1 envelope glycoprotein (Env) undergoes ordered conformational transitions after CD4 binding and co-receptor engagement during viral entry. While the physicochemical steps of viral entry are becoming defined, less is known about their immunochemical correlates and their roles as targets of protective antibodies. We describe studies that define the functional significance of epitope exposure during the first step of viral entry, the binding of gp120 to CD4. A panel of 41 human monoclonal antibodies (mAbs) were isolated that recognize epitopes which become exposed on trimeric Env only after CD4 engagement. These mAbs recognize clusters of epitopes mapping to three regions of gp120: a. Cluster A, the domain of gp120 occluded by interaction with gp41; b. Cluster B, a region proximal to the classical co-receptor binding site (CoRBS) involving the V1/V2 region; and Cluster C, the CoRBS. The mAbs were characterized for neutralization of Tier 1 and Tier 2 pseudoviruses and by antibody dependent cell mediated cytotoxicity (ADCC). mAbs recognizing all three clusters mediated ADCC but there was a strong bias in potency for mAbs that recognize Clusters A and B. Surprisingly, ADCC potency correlated inversely with CDR-H3 length but not with somatic hypermutation. By contrast, mAbs binding Cluster C epitopes were neutralizing but there was significant diversity in breadth and potency that correlated with epitope fine specificity and somatic hypermutation. ADCC potency did not correlate with neutralization breadth or potency. Thus, both neutralization and Fc-mediated effector function are co-selected with specificity but the nature of selection is distinct for these two anti-viral activities.





FIG. 1. Clinical parameters of subjects included in the analysis. The individual values of viremia and CD4 ϩ cell counts observed for the enrolled subjects are reported. Means and standard errors for each group (low-viremia and high-viremia) are shown. Ϫ ve, negative; ϩ ve, positive; n.a., not applicable. 
FIG. 2. Basal expression of activation markers and costimulatory molecules in CD14 ϩ cells (A to D). The basal expression of CD80, CD83, CD86, and HLA-DR on PBMCs was analyzed on fixed cells by using a FACScalibur flow cytometer, and data analysis was carried out using the FlowJo software program. PBMCs were gated for CD14 positivity. The MFI for each sample in each group is represented in both CD14 dim and CD14 hi gating. Means and standard errors for each group are shown. 
FIG. 3. Expression of activation markers and costimulatory molecules induced by HIV-VLPs in CD14 ϩ cells (A to D). PBMCs were incubated in the presence of HIV-VLPs for 16 h. The expression of CD80, CD83, CD86, and HLA-DR was analyzed on fixed cells by using a FACScalibur flow cytometer, and data analysis was carried out using the FlowJo software program. PBMCs were gated for CD14 positivity. The MFI for each sample in each group has been represented in both CD14 dim and CD14 hi gating. Means and standard errors for each group are shown. 
FIG. 4. n -fold induction of activation markers and costimulatory molecules by HIV-VLPs in CD14 ϩ cells (A to D). The n -fold increase in the MFI observed for each sample in each group after induction with HIV-VLPs, over the basal level (VLP versus PBS), is represented in both CD14 dim and CD14 hi gating. Means and standard errors for each group are shown. 
FIG. 5. Individual pattern of activation in CD14 dim cells. The expression of CD80, CD83, CD86, and HLA-DR in PBMCs was analyzed on fixed cells by using a FACScalibur flow cytometer, and data analysis was carried out using the FlowJo software program. The PBMCs were gated for CD14 dim positivity. Results of a representative experiment are shown; the shaded curve represents the baseline data for untreated cells. (A) Expression of markers in low-viremia group. (B) Expression of markers in high-viremia group. In each panel, the arrow indicates the samples with no induction of expression. 

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Th2 Polarization in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus (HIV)-Infected Subjects, as Activated by HIV Virus-Like Particles
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  • Full-text available

January 2009

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151 Reads

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36 Citations

We have recently shown that human immunodeficiency virus type 1 (HIV-1) Pr55(gag) virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A, induce maturation and activation of monocyte-derived dendritic cells (MDDCs) with a production of Th1- and Th2-specific cytokines. Furthermore, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4(+) T cells in an ex vivo immunization assay. In the present study, we show that similar data can be obtained directly with fresh peripheral blood mononuclear cells (PBMCs), and the HIV-1 seropositivity status, with either low or high viremia, does not significantly impair the immune activation status and the responsiveness of circulating monocyte CD14(+) cell populations to an immunogenic stimulus. Some HIV-1-seropositive subjects, however, show a complete lack of maturation induced by HIV-VLPs in CD14(+) circulating cells, which does not consistently correlate with an advanced status of HIV-1 infection. The established Th2 polarization in both HIV-seropositive groups is efficiently boosted by HIV-VLP induction and does not switch into a Th1 pattern, strongly suggesting that specific Th1 adjuvants would be required for therapeutic effectiveness in HIV-1-infected subjects. These results indicate the possibility of screening PBMCs for donor susceptibility to an immunogen treatment, which would greatly simplify the identification of "responsive" vaccinees as well as the understanding of eventual failures in individuals enrolled in clinical trials.

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Reverse Transcriptas

September 2008

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42 Reads

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3 Citations

Critical Reviews in Biochemistry and Molecular Biology

Abstract Recognition of RNA tumor viruses as causative agents of malignant disease started with the observation (by Ellerman and Bang in 1908) that a filterable agent transmitted avian leukemia1 and the subsequent isolation of chicken sarcoma virus by Rous in 1911.2 These findings were followed by an intense and continuous search for new isolates, the establishment of inbred strains of mice, and the development of tissue culture techniques. In the early 1960s, the significance of RNA tumor viruses was generally accepted, especially in avian and murine systems, but with some skepticism, probably because its role in natural disease was not yet evident. Moreover, the mode of replication of the RNA tumor viruses was still not understood. In recent years, the study of these viruses markedly intensified, principally because of a discovery which filled a major gap in the understanding of their replication. This is the independent discovery of the viral RNA-dependent DNA polymerase (reverse transcriptase) by Temin and Mizutani3 and by Baltimore4 in 1970. This discovery also extended our understanding of the mode of genetic information transfer, and it paved the way for the finding of viral-related components, reverse transcriptase5-11 and type-C viral related nucleic acids in human leukemic cells by Gallo, Spiegelman, and their co-workers (see later section10,12-17).


Importance of a therapeutic vaccination among the HIV infected patients under antiretroviral treatment

December 2006

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9 Reads

Bulletin de l Académie Nationale de Médecine

Tat is a transactivator protein coded by the genome of HIV-1. Besides its transactivating activity, Tat is also exported outside the infected cell and acts as an immunosuppressive agent inducing apoptosis of non-infected activated T-cells and release of α-interferon and TNFα by dendritic cells. The latter properties suggest that Tat is a potential target for an AIDS vaccine. Hereafter we present the data of a two years analytical antiretroviral treatment interruption study carried out in patients who had completed a Phase 1/2 double blind placebo controlled vaccine trial using a non toxic and immunogenic Tat derivative called Tat Toxoid. Six of twelve patients who received Tat toxoid adjuvanted in DcChol mounted a stong neutralizing antibody reaction to Tat. All the six vaccine responders remained medication-free at least two years. By contrast the majority of non-reponders who received the vaccine or the placebo preparation resumed HAART during the two years follow-up study. Such results seem to justify a large scale vaccination trial in the near future.


FIG. 1. Evaluation of monocyte purity. Human peripheral blood mononuclear cells, isolated by Ficoll-Hypaque density gradient centrifugation, were enriched for CD14 monocytes by negative selection. The purity of the obtained monocyte population was evaluated by flow cytometry using MAbs specific for the indicated cellular markers.
FIG. 2. Maturation of DCs by baculovirus-expressed HIV-VLPs. Immature MDDCs were incubated in the presence of the indicated stimulus for 16 h. (A) The expression of CD80, CD83, CD86, and HLA-DR was analyzed on fixed cells by FACScalibur flow cytometer, and data analysis was carried out with FlowJo software. The results of one representative experiment out of five are shown; the shaded curve represents the background fluorescence, and the dotted line indicates the peak LPS response. (B) The level of cytokines in the culture supernatant was measured by ELISA. The results represent the average of five experiments. 
FIG. 3. Surface TLRs do not mediate the maturation of DCs by baculovirus-expressed HIV-VLPs. Immature MDDCs were preincubated for 1 h with purified anti-TLR2 (TL2.1, IgG2a) and anti-TLR4 (HT125, IgG2a) or an unrelated control IgG2a (15 ␮ g/ml) and then with HIV-VLPs (10 ␮ g/ml). (A) After 16 h, the expression of CD80, CD83, CD86, and HLA-DR was analyzed on fixed cells by FACScalibur flow cytometer and data analysis was carried out with FlowJo software. The results of one representative experiment out of three are shown. The shaded curve represents the untreated cells; the gray curves represent the cells treated in the presence of the MAbs. (B) The level of cytokines in the culture supernatant was measured by ELISA and is expressed as percentage of production in the presence of the anti-TLR2 and -4 antibodies, compared to cells treated with the unrelated control IgG2a. The results represent the average of three experiments. 
FIG. 4. Uptake of baculovirus-expressed HIV-VLPs by MDDCs. CFDA-labeled HIV-VLPs were loaded on immature MDDCs, untreated or preincubated for 1 h with cytochalasin D (1 ␮ M) or DC-SIGN ligand Man9 (200 nM). DCs were collected after 2 and 24 h and observed under a fluorescence microscope (panels A and B); in parallel, aliquots of cell culture were collected and fixed with paraformaldehyde for measurements by flow cytometry (C). The shaded curve represents the background, the black curve represents the cells loaded with CFSE-labeled HIV-VLPs without inhibitors, and gray curves represent the cells preincubated with inhibitors and then loaded with CFSE-labeled HIV-VLPs (dark gray, Man9; light gray, cytochalasin D). The MFIs of cells with different treatments are shown in arbitrary units in panel D. 
Baculovirus-Derived Human Immunodeficiency Virus Type 1 Virus-Like Particles Activate Dendritic Cells and Induce Ex Vivo T-Cell Responses

January 2006

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102 Reads

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123 Citations

We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model based on HIV-1 Pr55gag virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A (HIV-VLPAs). The HIV-VLPAs show the induction in BALB/c mice of systemic and mucosal neutralizing antibodies as well as cytotoxic T lymphocytes, by intraperitoneal as well as intranasal administration. In the present article, the effects of the baculovirus-expressed HIV-VLPs on human immature monocyte-derived dendritic cells (MDDCs) have been evaluated. The HIV-VLPs efficiently induce maturation and activation of MDDCs and are incorporated into MDDCs preferentially via an actin-dependent macropinocytosis and endocytosis. The HIV-VLP-activated MDDCs show enhanced Th1- and Th2-specific cytokine production, and the effects of HIV-VLPs on MDDCs are not mediated through Toll-like receptors 2 and 4 (TLR2 and -4) signaling. Finally, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4+ T cells in an ex vivo immunization assay. Our results on the interaction and processing of baculovirus HIV-VLPs by MDDCs give an insight into the mechanisms underlying the immune response induced by HIV-VLPAs in vivo.


Citations (64)


... The presence of viral DNA in serum/plasma has been used as a marker for active viral infection [29][30]. The herpesviruses have DNA genomes and because they need to infect cells for replication, extracellular viral DNA most probably denotes assembled virions, liberated from cells for further [19] reported HHV-6 DNA absent in the serum from both patients with MS and with OND. ...

Reference:

Human herpesvirus-6 and the etiology of multiple sclerosis: A literature review
Quantitative PCR for human herpesviruses 6 and 7
  • Citing Article
  • August 1995

... This type of angioproliferative disease nowadays represents one of the most aggressive type of tumors in HIV-1-infected individuals [66]. It was demonstrated that primary lesions of KS express a very high level of CD13/APN and this contributes to the enhanced vascularization of the tumor [22,67]. Our attention in the present study is also focused on a colon carcinoma tumor model which is one of the most lethal forms of tumor in developed countries. ...

Identification and culture of Kaposi's sarcoma-like spindle cells from the peripheral blood of human immunodeficiency virus-1-infected individuals and normal controls [see comments]
  • Citing Article
  • October 1994

Blood

... G ammaherpesviruses are ubiquitous pathogens that infect a majority of the adult population and are associated with several malignancies, including B cell lymphomas (1). The two known human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) (2,3), establish lifelong infection of hematopoietic cells, including B cells and macrophages. Gammaherpesviruses manipulate B cell differentiation to establish latency in long-lived memory B cells (4)(5)(6). ...

Identification and culture of Kaposi's sarcoma-like spindle cells from the peripheral blood of human immunodeficiency virus-1-infected individuals and normal controls [see comments]
  • Citing Article
  • October 1994

Blood

... Restrictions on freedom of movement ensured that few people entered or exited the country; indeed, sexual contact with foreignersusually while serving the state abroadwas initially considered the single greatest risk factor for HIV. 101 Today, such restrictions would be less practicable, particularly given Cuba's popularity as a tourist destination. Tourists, even those arriving for the explicit purpose of sexual contact with locals, have never been subject to similar scrutiny. ...

Human immunodeficiency virus
  • Citing Article
  • January 2010

... Only one preparation, which in vitro had the most activity against KS sarcoma cell lines was selected for clinical investigation. The hCG given intralesionally-induced dose-dependent tumor regression and apoptotic cell death in up to 83% of treated KS lesions [106]. A subsequent phase I study was conducted using subcutaneous injections of hCG at the dose levels of 5000 IU daily, or 10,000 IU three times weekly [107]. ...

Human chorionic gonadotropin has antitumor activity in AIDS-related Kaposi's sarcoma
  • Citing Article
  • January 1996

... Antisense oligonucleotides such as MG98 and ISIS 5132, designed to inhibit the biosynthesis of DNA methyltransferase and c-raf kinase respectively, are in human clinical trials for cancer (Mardan et al. 2002). Synthetic antisense DNA oligonucleotides and oligonucleotide analogs (Agarawal and Tang 1992), which inhibit the replication of several infectious agents such as hepatitis C virus (Alt et al. 1995), human cytomegalovirus (Azad et al. 1993), human immunodeficiency virus, and papilloma virus (Bordier et al. 1992;Cowsert et al. 1993;Gerviax et al. 1997;Hanecak et al. 1996;Kinchington et al. 1992;Lisziewicz et al. 1992Lisziewicz et al. , 1993Mirabelli et al. 1991;Morvan et al. 1993;Tonkinson and Stein 1993), have also been designed. ...

GEM-91 - ANTISENSE OLIGONUCLEOTIDE BASED THERAPEUTIC AGENT FOR AIDS
  • Citing Article
  • August 1994

AIDS Research and Human Retroviruses

... Nigeria has one-third of African total population and the human immunodeficiency virus (HIV) prevalence of 4.1%. 1 The official HIV prevalence in Nigeria is 3.2%. 2 The spread of HIV among neonates and infant largely depends on their mother's status during pregnancy and lactation. ...

HIV-1, not HIV-2, is prevalent in Nigeria: Need for consideration in vaccine plans
  • Citing Article
  • January 1994

... These ®ndings support the view that the different epidemiologic forms of KS represent a uniform disease spectrum with common pathogenic denominators and indicate that invasion into surrounding dermis may be a crucial step in the pathogenesis of the tumor. Although HIV-1 Tat protein is a wellknown promotor of KS cell invasion and migration (Colombini et al, 1998), these observations also suggest that KS-derived spindle cells have intrinsic invasive properties independently of HIV products. The invading spindle cells had a phenotype similar to that VOL. ...

HIV-1 Tat protein enhances angiogenesis and Kaposi's sarcoma (KS) development triggered by inflammatory cytokines (IC) or bFGF by engaging theαvβ3 integrin
  • Citing Article
  • April 1997

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology

... HHV-8 was therefore assigned to the g-herpes virus group. Previous studies of HD cases by polymerase chain reaction (PCR) for the detection of virus DNA showed either absence [17] or a low frequency of HHV-6 in HD [18]; whereas other investigators found up to 70% of HD cases to be associated with HHV-6 [19]. However, these studies did not address questions as to differentiation between HHV-6 and HHV-7 as well as co-infection with EBV and CMV and HHV-8. ...

High prevalence of human herpes virus 6 DNA in Hodgkin's disease: a study by in situ hybridization and polymerase chain reaction
  • Citing Article
  • March 1995

Current Diagnostic Pathology

... The virus inhibition is mediated by the synergistic effect of the three b-chemokines: MIP-1a (CCL3), MIP-1b (CCL4), and RANTES (CCL5) (at 500-pg to 500-ng concentrations) (194). Indeed, only when a combination of antibodies to the three b-chemokines is used is the previously observed viral inhibition reversed (283,284). Notably as well, CCL5 activity in monocytes/macrophages is optimal when the chemokine is in complex with proteoglycans (202). ...

Role of Chemokines in Suppressing HIV Replication
  • Citing Article
  • November 1996

Science