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Background: APOBEC3/Rfv3 restricts acute Friend retrovirus (FV) infection and promotes virus-specific neutralizing antibody (NAb) responses. Classical Rfv3 studies utilized FV stocks containing lactate-dehydrogenase elevating virus (LDV), a potent type I interferon inducer. Previously, we showed that APOBEC3 is required for the anti-FV activity of exogenous IFN-alpha treatment. Thus, type I interferon receptor (IFNAR) signaling may be required for the APOBEC3/ Rfv3 response. Results: To test if the APOBEC3/Rfv3 response is dependent on type I IFN signaling, we infected IFNAR knockout versus IFNAR/APOBEC3 double-knockout mice with FV/LDV or LDV-free FV, and evaluated acute FV infection and subsequent NAb titers. We show that LDV co-infection and type I IFN signaling are not required for innate APOBEC3- mediated restriction. By contrast, removal of LDV and/or type I IFN signaling abrogated the APOBEC3-dependent NAb response. Conclusions: APOBEC3 can restrict retroviruses in a type I IFN-independent manner in vivo. By contrast, the ability of APOBEC3 to promote NAb responses is type I IFN-dependent. These findings reveal novel insights on the interplay between type I IFNs and APOBEC3 in vivo that may have implications for augmenting antiretroviral NAb responses. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Non-neutralizing IgG anti-PID antibodies decreased viral load following high dose vaginal challenge of non-human primates," by C. Moog and colleagues are presented.

Background: Human T cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), which is encoded by a minus strand mRNA, is thought to play important roles in the development of adult T-cell leukemia (ATL) and HTLV- 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive analysis of HBZ, including mRNA and protein expression, humoral immunoreactivity against HBZ, and HTLV-1 proviral load (PVL), in HTLV- 1-infected individuals with different clinical status has not been reported previously. Results: In this study, using novel monoclonal antibody-based in-house enzyme-linked immunosorbent assay systems, we report the absolute quantification of HBZ protein and its plasma antibody in clinical samples from HTLV-1-infected individuals with different clinical status. The data were compared to both HBZ mRNA levels and PVL. The results showed that plasma anti-HBZ antibody was detectable only in 10.4 % (5/48) of asymptomatic carriers (ACs), 10.8 % (13/120) of HAM/TSP patients, and 16.7 % (7/42) of ATL patients. HBZ protein was detected in three out of five patients with acute ATL, but was not detected in patients with HAM/TSP (0/10) or ACs (0/4). Thus, an antibody response to HBZ was not associated with the PVL or the expression of HBZ (both at the mRNA and protein levels) or the clinical status of the infection. Conclusions: The present results emphasize the extremely low expression and immunogenicity of HBZ in natural HTLV-1 infection. However, there is a possibility that the low but distinct expression of HBZ protein in PBMCs is associated with the survival of HTLV-1-infected cells and the development of ATL. [ABSTRACT FROM AUTHOR]

Background Human T-cell leukemia virus type 1 (HTLV-1) causes both neoplastic and inflammatory diseases, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Because these life-threatening and disabling diseases are not yet curable, it is important to prevent new HTLV-1 infections. Findings In this study, we have established a simple humanized mouse model of HTLV-1 infection for evaluating prophylactic and therapeutic interventions. In this model, HTLV-1-negative normal human peripheral blood mononuclear cells (PBMCs) are transplanted directly into the spleens of severely immunodeficient NOD-SCID/γcnull (NOG) mice, together with mitomycin-treated HTLV-1-producing T cells. Using this model, we tested the efficacy of monoclonal antibodies (mAbs) specific to HTLV-1 as well as human IgG isolated from HAM/TSP patients (HAM-IgG) in preventing HTLV-1-infection. One hour before and 24 h after transplantation of the human cells, each antibody sample was inoculated intraperitoneally. On day 14, human PBMCs isolated from the mouse spleens were tested for HTLV-1 infection. Whereas fresh CD4-positive and CD8-positive T cells isolated from untreated mice or mice treated with isotype control mAb, HTLV-1 non-neutralizing mAbs to envelope gp46, gag p19, and normal human IgG were all infected with HTLV-1; the mice treated with either HTLV-1 neutralizing anti-gp46 mAb or HAM-IgG did not become infected. Conclusions Our data indicate that the neutralizing function of the antibody, but not the antigen specificity, is essential for preventing the in vivo transmission of HTLV-1. The present animal model will also be useful for the in vivo evaluation of the efficacy of candidate molecules to be used as prophylactic and therapeutic intervention against HTLV-1 infection. [ABSTRACT FROM AUTHOR]

Background Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by ×4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than ×4 isolates, both autologous and heterologous. Child 2 raised a weak ×4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-×4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Glycans on the human immunodeficiency virus (HIV) envelope glycoprotein (Env) play an important role in viral infection and evasion of neutralization by antibodies. In this study, all 25 potential N-linked glycosylation sites (PNGS) on the HIV-1 CRF07_BC Env, FE, were mutated individually to study the effect of their removal on viral infectivity, virion production, and antibody-mediated neutralization. Results: Removal of specific N-glycosylation sites has a significant effect on viral infectivity and antibody-mediated neutralization phenotype. Six of these glycosylation mutants located on the V1/V2 and C1/C2 domains lost infectivity. PNGS mutations located on V4/C4/V5 (except N392 on V4), were shown to increase viral infectivity. Furthermore, FE is much more dependent on specific glycans than clade B Env YU-2. On neutralization effect, PNGS mutations at N197 (C2), N301 (V3), N442 (C4) and N625 (gp41) rendered the virus more susceptible to neutralization by the monoclonal antibodies (MAbs) that recognize the CD4 binding site or gp41. Generally, mutations on V4/V5 loops, C2/C3/C4 regions and gp41 reduced the neutralization sensitivity to PG16. However, mutation of N289 (C2) made the virus more sensitive to both PG9 and PG16. Furthermore, we showed that mutations at N142 (V1), N355 (C3) and N463 (V5) conferred resistance to neutralization by anti-gp41 MAbs. We used the available structural information of HIV Env and homology modeling to provide a structural basis for the observed biological effects of these mutations. Conclusions: This report provides the first systematic experimental account of the biological role of the entire PNGS on an HIV-1 Env, which should provide valuable insights for understanding the function of Env in HIV infection cycle and for developing future anti-HIV strategies. [ABSTRACT FROM AUTHOR]

Background: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1 -infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system Results: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4+ T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients. Conclusions: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Vector induced skewing of antibody Fc-effector functions," by A. Chung and colleagues is presented.

An abstract of the conference paper "DNA vaccines that express the MPER of HIV-1 gp41 elicit different antibodies depending upon their transmembrane and cytoplasmic domain," by J. K. Scott and colleagues is presented.

An abstract of the conference paper "Structural definition of a novel CD4-induced epitope that is targeted by a single-headed immunoglobulin to effect broad and potent HIV neutralization," by P. Acharya and colleagues is presented.

An abstract of the conference paper "Native envelope-based immunogens derived from critical timepoints in the development of breadth elicit rapid neutralizing antibodies in rabbits," by D. C. Malherbe and colleagues is presented.

An abstract of the research paper "Straightforward selection of broadly neutralizing single-domain antibodies targeting the conserved CD4 and co-receptor binding sites of HIV-1 gp120," by J. Matz and colleagues is presented.

An abstract of the research paper "Biodistribution of neutralizing monoclonal antibodies IgG1 b12 and LALA in mucosal and lymphatic tissues of rhesus macaques," by A. J. Hessell and colleagues is presented.

An abstract of the conference paper "Developing a quantitative model of antibody effector function," by A. W. Boesch and M. Ackerman is presented.

An abstract of the conference paper "Intrasubtype C superinfected individuals mount delayed and low-titer autologous neutralizing antibody responses prior to superinfection," by D. Basu and colleagues is presented.

An abstract of the research paper "Mutations in the V1 domain of Thai CRF01-AE viruses that confer sensitivity/resistance to broadly neutralizing antibodies," by S. O'Rourke and colleagues is presented.

An abstract of the research paper "V1/V2-directed antibodies elicited in RV144 vaccinees bind to a structurally polymorphic site," by J.S. McLellan and colleagues is presented.

An abstract of the research paper "Light chain plays a role in neutralizing antibody in b12 H chain knock-in mouse," by T. Ota is presented.

An abstract of the research paper "Sequential exposure to specific antibody escape mutations may program neutralization breadth during subtype A HIV-1 infection," by M.K. Murphy and colleagues is presented.

An abstract of the research paper "Antibody responses to V2 loop are induced by CRF01_A E and not Clade B envelopes," by N. Karasawas and colleagues is presented.

An abstract of the research paper "Mapping epitopes on CRF01_AE viruses recognized by broadly neutralizing antibodies in sera from elite neutralizers from North America and Thailand," by S.M. O'Rourke and colleagues is presented.

An abstract of the research paper "Recombinant Env proteins that bind the quaternary-specific, V1/V2-directed PGT antibodies," by J. Gorman and colleagues is presented.

An abstract of the research paper "A novel rabbit monoclonal antibody platform to dissect the diverse repertoire of antibody epitopes for HIV-1 Env immunogen design," by Y. Chen and colleagues is presented.

An abstract of the conference paper "Neutralizing and Non-Neutralizing Antibody Responses in HIV-1 Subtype C Chronically Infected Patients With Divergent Rates of Disease Progression," by D. Archary and colleagues is presented.

An abstract of the research paper "Antibody subclass skewing predicts enhanced ADCC activity in both natural infection and vaccination," by A. Chung and colleagues is presented.

An abstract of the conference paper "Refined Identification of Neutralization-Resistant CRF02-AG Viruses and Their Sensitivity to Anti-MPER Neutralizing Antibodies," by R. A. Jacob and colleagues is presented.

An abstract of the conference paper "Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies From an HIV-1 Vaccine Efficacy Trial Preferentially Use the VH1 Gene Family," by M. Bonsignori and colleagues is presented.

An abstract of the conference paper "HIV-1 envelope trimer elicits higher neutralizing antibody responses than monomeric gp120" by J. M. Kovacs and colleagues is presented.

An abstract of the conference paper "Hyperglycosylated gp120 Mutants Elicit Improved CD4-Binding Site Directed Antibodies in a Heterologous Prime:Boost Regimen," by F.K. Ahmed and colleagues is presented.

An abstract of the conference paper "Characteristics of HIV-1 gp120 Molecules That Bind Ancestor, Intermediate and Mature Forms of VRC01-Like Antibodies," by M. Joyce and colleagues is presented.

An abstract of the conference paper "Superinfection by Discordant Subtypes of HIV-1 Does Not Enhance the Neutralizing Antibody Response Against Autologous Virus," by L.M. Mayr and colleagues is presented.

An abstract of the conference paper "Optimization and Validation of the HIV-1 Neutralizing Antibody Assay in A3R5 Cells," by M. Sarzotti-Kelsoe and colleagues is presented.

An abstract of the conference paper "Detection of Antibodies to the a4b7 Integrin Binding Site on HIV-1 gp120 V2 Loop Using a Novel Cell Adhesion Assay," by M. Rao and colleagues is presented.

An abstract of the conference paper "Biophysical Dissection of the Antigen-Antibody Interaction of the Broadly Reactive Anti-V3 Human mAb 447-52D," by A. Killikelly and colleagues is presented.

An abstract of the conference paper "Construction and Characterization of Neutralizing Antibody Fragments for Efficient Access to V3 Epitope," by Y. Maruta and colleagues is presented.

An abstract of the conference paper "Affinity Maturation Pathway of an Anti-MPER Neutralizing mAb, CAP206-CH12," by N.L. Tumba and colleagues is presented.

An abstract of the conference paper "Comparison of the Neutralization Sensitivity of South African and Indian HIV-1 Subtype C Viruses to South African Plasma Antibodies," by T. Hermanus and colleagues is presented.

An abstract of the conference paper "Neutralizing Anti-HIV Antibodies Develop in a Humanized Mouse Model of HIV-1 Infection," by E. Seung and colleagues is presented.

An abstract of the conference paper "Structural Definition for a New Modality of Broad and Potent Antibody Neutralization at the CD4-Binding Site on HIV-1 gp120," by T. Zhou and colleagues is presented.

An abstract of the conference paper "Residue 315 Regulates V3 Exposure and V3 Antibody Recognition on HIV Subtype B and C Viruses," by S. Manhas and colleagues is presented.

An abstract of the conference paper "Plasma Antibodies That Cross React to Subtype-B and C Third Variable (V3) Region Develop in Indian HIV-1 Infected Individuals With Time," by S. Andrabi and colleagues is presented.

An abstract of the conference paper "Design of Epitope-Specific Probes for Sera Analysis and Antibody Isolation," by I. Georgiev and colleagues is presented.

An abstract of the conference paper "Recognition and Penetration of the HIV-1 Env Glycan Shield by Potent Broadly Neutralizing Antibodies," by J. Julien and colleagues is presented.

An abstract of the conference paper "Neutralization and Enhancement of Trans Infection by Erythrocyte-Bound HIV With Antibodies and Complement," by Z. Beck and colleagues is presented.

An abstract of the conference paper "Comprehensive Mapping of SIVmac239 Envelope Antigenic Determinants Recognized by Specific Polyclonal Antibodies in Vaccinated and/or Infected Macaques," by J. Guo and colleagues is presented.

An abstract of the conference paper "The Breadth of Maternal HIV-1 Specific Neutralizing Antibodies Is Not Associated With a Lower Risk of Mother-to-Infant Transmission," by A. Chaillon and colleagues is presented.

An abstract of the conference paper "Characterization in Rabbits & Nonhuman Primates of the Neutralizing Antibody Response Elicited by DNA & Protein Vaccination With SIVmac251 & SIVsmE660," by V.P. Menon and colleagues is presented.

An abstract of the conference paper "Assessing the Protective Efficacy of Antibodies to the HIV gp41 Region by Active Vaccination," by S.K. Sharma and colleagues is presented.

An abstract of the conference paper "Hyperglycosylated Resurfaced Stabilized GP120 Core As an Immunogen Elicits Antibodies Targeted at the CD4-Binding Site" by K. Dai and colleagues is presented.

An abstract of the conference paper "Neutralizing Antibodies Elicited in Rabbits by Patient-Derived Env Trimer Immunization" by L. Heyndrickx and colleagues is presented.