A5018205846- HIV Research and Treatment
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- HIV/AIDS drug development and treatment
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- vaccines and immunoinformatics approaches
- Microbial infections and disease research
- Viral gastroenteritis research and epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- CAR-T cell therapy research
- Viral-associated cancers and disorders
- Mosquito-borne diseases and control
- Hematopoietic Stem Cell Transplantation
- Reproductive tract infections research
- Counseling Practices and Supervision
- Virology and Viral Diseases
- Immune Response and Inflammation
- Poxvirus research and outbreaks
Emory University
2014-2023
Emory National Primate Research Center
2014-2017
Harvard University
2006-2017
New England Biolabs (United States)
2003-2017
Primate Conservation
2005-2016
Ragon Institute of MGH, MIT and Harvard
2009-2016
Massachusetts General Hospital
2000-2014
Harvard University Press
1994-2008
Georg Speyer Haus
2007
National Institutes of Health
2007
Human and simian immunodeficiency virus (HIV SIV) replicate optimally in activated memory CD4 + T cells, a cell type that is abundant the intestine. SIV infection of rhesus monkeys resulted profound selective depletion cells intestine within days infection, before any such changes peripheral lymphoid tissues. The loss occurred coincident with productive large numbers mononuclear at this site. appears to be major target for replication site early infection.
Although CD8+ lymphocytes in human immunodeficiency virus type 1 (HIV-1)-infected individuals have been demonstrated to suppress viral replication, the mechanisms of inhibition not defined precisely. A large body evidence indicates that these cells act via soluble inhibitory factors, but potential role HLA class I-restricted cytolysis has remained controversial. Here we demonstrate HIV-1-specific cytotoxic T (CTL) mediate antiviral suppression by both cytolytic and noncytolytic mechanisms....
Abstract Although vigorous activated and memory CTL have been associated with HIV-1 infection, data are lacking regarding the breadth of epitopes recognized in a given individual relationship to viral quasispecies present vivo. In this study we performed detailed analysis HIV-1-specific response seropositive person documented infection 15 yr duration, stable CD4 counts above 500 cells/ml, load persistently below molecules RNA/ml plasma. Epitope mapping studies revealed presence HLA class...
A herpesvirus that is related to but distinct from the Kaposi's sarcoma-associated (KSHV, or human 8) was isolated rhesus monkeys. The sequence of 10.6 kbp virion DNA revealed presence an interleukin-6 homolog similar what present in KSHV and a closer relatedness polymerase glycoprotein B reading frames those than any other herpesvirus. This monkey replicated lytically high titers cultured fibroblasts. Antibody testing prevalence for at least 10 years our colony two colonies were tested....
Human immunodeficiency virus 1 (HIV-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using freshly isolated peripheral blood mononuclear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-1-specific CTL have been defined, the effector mediating this characterized less well. Specifically, no studies addressed breadth duration to defined epitope. In present study, longitudinal...
ABSTRACT Deletion mutants of the pathogenic clone simian immunodeficiency virus isolate 239 (SIVmac239) were derived that are missing nef , vpr and upstream sequences (US) in U3 region LTR (SIVmac239Δ3), vpx US (SIVmac239Δ3x), (SIVmac239Δ4). These multiply deleted derivatives replicated well continuously growing CEMx174 cell line infectious for rhesus monkeys. However, on basis load measurements, strength antibody responses, lack disease progression, these highly attenuated. Measurements...
ABSTRACT We examined the ability of a live, attenuated deletion mutant simian immunodeficiency virus (SIV), SIVmac239Δ3, which is missing nef and vpr genes, to protect against challenge by heterologous strains SHIV89.6p SIVsmE660. pathogenic, recombinant SIV in envelope gene has been replaced human type 1 gene; other structural genes are derived from SIVmac239. SIVsmE660 an uncloned, independent isolate same primate lentivirus subgrouping as SIVmac but with natural sequence variation all...
Numerous studies of human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) have examined their ability to recognize B-cell lines expressing recombinant HIV-1 proteins, but relatively few data regarding the lysis HIV-1-infected cells by CTL are available. We studied HIV-1-specific clones defined epitope specificity and HLA restriction lyse infected CD4+ at serial time points following infection. cell were acutely with IIIB a high multiplicity infection, kinetics...
Abstract The majority of immunogenic CTL epitopes bind to MHC class I molecules with high affinity. However, peptides longer or shorter than the optimal epitope rarely Therefore, identification from pathogens may ultimately be critical for inducing strong responses and developing epitope-based vaccines. SIV-infected rhesus macaque is an excellent animal model HIV infection humans. Although a number have been mapped in macaques, not well defined, their anchor residues are unknown. We now...
We have established long-term cultures of several cell lines stably and uniformly expressing human immunodeficiency virus type 1 (HIV-1) in order to (a) identify naturally processed HIV-1 peptides recognized by cytotoxic T lymphocytes (CTL) from HIV-1-seropositive individuals (b) consider the hypothesis that occurring epitope densities on HIV-infected cells may limit their lysis CTL. Each two A2-restricted CD8+ CTL specific for gag or reverse transcriptase (RT) a single peptide...
ABSTRACT Three different deletion mutants of simian immunodeficiency virus (SIV) that vary in their levels attenuation were tested for the ability to protect against mucosal challenge with pathogenic SIV. Four female rhesus monkeys vaccinated by intravenous inoculation SIVmac239Δ3, four SIVmac239Δ3X, and SIVmac239Δ4. These three vaccine strains exhibit increasing attenuation: Δ3 < Δ3X <Δ4. The challenged vaginal exposure uncloned, SIVmac251 at 61 weeks after time vaccination. On basis...
CTL directed at the highly conserved HIV-1 gag protein have been described in seropositive persons and may be an important host defense against this retrovirus. Presently only limited data are available regarding specific epitopes recognized by these CTL. In study, we performed a detailed examination of gag-specific response three subjects, using both unstimulated PBMC cloned Lysis gag-expressing targets was found to mediated CD3+CD8+ lymphocytes restricted class I Ag. Multiple Ag were...
Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms protection by live-attenuated may provide important insights into immune responses needed for HIV-1. Here we investigated development antibodies that are functional neutralization-resistant strains, and tested hypothesis these associated with protection. In absence detectable neutralizing antibodies,...
Zika virus infection early after birth has deleterious effects on the developing brain and long-term behavioral changes in rhesus macaques.
Epstein-Barr virus (EBV) is a human lymphocryptovirus that causes infectious mononucleosis, persists asymptomatically for life in nearly all adults, and associated with the development of B cell lymphomas nasopharyngeal carcinomas. A highly similar rhesus naturally endemic monkeys was used to orally infect naı̈ve animals from pathogen-free colony. This animal model reproduced key aspects EBV infection, including oral transmission, atypical lymphocytosis, lymphadenopathy, activation CD23 +...
Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and sequence variation remains controversial. We analyzed HLA-A*0201 restricted responses in 17 HIV-1-infected individuals with loads ranging from < 400 221,000 HIV RNA molecules per milliliter plasma. In 13 out infected subjects, CTL against SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other epitopes (ILKEPVHGV, IV9; VIYQYMDDL, VL9) only...
Although live attenuated vaccine strains of simian immunodeficiency virus (SIV) have proven highly effective in protecting macaques against challenge with pathogenic SIV strains, little is known about the mechanisms protective immunity induced by these vaccines. We examined cytotoxic T-lymphocyte (CTL) responses animals infected SIVmac239delta nef (deficient nef) or 3 nef, vpr, and upstream sequences U3). To enhance detection SIV-specific CTL activity, we stimulated peripheral blood...
Although the immunologic basis of protective immunity in human immunodeficiency virus type 1 (HIV-1) infection has not yet been defined, virus-specific cytotoxic T lymphocytes (CTL) are likely to be an important host defense and may a critical feature effective vaccine. These observations, along with inclusion HIV-1 envelope majority vaccine candidates presently clinical trials, underscore importance precise characterization cellular immune responses this protein. humoral protein have...
Human immunodeficiency virus type 1 (HIV-1) infection is associated with elevated levels of inflammatory cytokines in the serum and cerebrospinal fluid infected persons, but sources these proteins as well specific stimuli which trigger their production release have not been fully defined. In this study, we evaluated ability HIV-1-specific cytotoxic T-lymphocyte (CTL) clones derived from seropositive persons to gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), TNF-beta...
Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human challenges, the specific immune responses that confer this have not been determined. To test whether cellular mediated by CD8+ lymphocytes contribute to vaccine-induced protection, we depleted rhesus macaques vaccinated with SIVmac239Delta3 of then challenged them SIVmac251 intravenous route. While vaccination did prevent infection pathogenic challenge virus,...
In April 2006, the National Institute of Allergy and Infectious Disease (NIAID)-funded HIV Vaccine Trials Network NIAID Division AIDS sponsored a workshop at which nonhuman primate (NHP) researchers clinical trial scientists with vaccine research expertise discussed how to more effectively use NHPs for evaluating HIV-1 candidates. This precipitated broad discussion on what types NHP studies should be targeted in critical preclinical pathway candidates, especially those designed elicit...
Type I interferons (IFN-I) are critical mediators of innate control viral infections but also drive the recruitment inflammatory cells to sites infection, a key feature severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe respiratory syndrome 2) infection using mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown reduce binding endogenous IFN-I. IFNmod treatment uninfected RMs observed...