A5044801294- HIV Research and Treatment
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Virology and Viral Diseases
- Bacteriophages and microbial interactions
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Animal Disease Management and Epidemiology
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 detection and testing
- Glycosylation and Glycoproteins Research
- Infant Nutrition and Health
- Polyomavirus and related diseases
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- Calcium signaling and nucleotide metabolism
- COVID-19 Impact on Reproduction
- Viral Infections and Outbreaks Research
Kumamoto University
2015-2024
Kaketsuken (Japan)
2024
ORCID
2020
National Institute of Allergy and Infectious Diseases
2006-2009
National Institutes of Health
2007-2009
Johns Hopkins University Center for AIDS Research
2009
Kyoto University
1997-2007
The University of Tokyo
1996
Tokyo University of Science
1996
German Primate Center
1996
Administration of convalescent plasma or neutralizing monoclonal antibodies (mAbs) is a potent therapeutic option for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection. However, SARS-CoV-2 variants with mutations in the spike protein have emerged many countries. To evaluate efficacy induced patients against emerging variants, we isolate anti-spike mAbs from two COVID-19 infected prototypic single-cell sorting immunoglobulin-G-positive (IgG
We constructed a series of human immunodeficiency virus 1 (HIV-1)/simian strain mac (SIVmac) chimeric viruses having vpr and/or nef genes either HIV-1 or SIVmac based on with LTRs, gag, pol, vif and vpx derived from tat, rev, vpu env HIV-1. All the replicated in macaque peripheral blood mononuclear cells (PBMCs) several CD4+ cell lines, though their growth potentials were slightly different depending whether SIVmac, defective. The presence accelerated replication all used each chimera...
A chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu, env, nef genes of type 1 was generated. The virus, NM-3n, grew competently in peripheral blood mononuclear cells from cynomolgus monkeys like parental SIVmac. Two one rhesus monkey inoculated with NM-3n raised antibodies to SIVmac Gag HIV-1 Env. persisted for at least 1.7 years. contained neutralizing activity not only original but also HIV-1. Infectious viruses were isolated 37 63 weeks after inoculation...
The progressive decline of CD4(+) T cells is a hallmark disease progression in human immunodeficiency virus (HIV) and simian (SIV) infection. Whereas the acute phase infection dominated by virus-mediated depletion memory cells, chronic often associated with total including naïve subset. mechanism this second cell loss unclear may include immune activation-induced death, immune-mediated destruction, regenerative or homeostatic failure. We studied patterns subset blood tissues group 20 rhesus...
Simian immunodeficiency virus (SIV) infection of rhesus macaques has become an important surrogate model for evaluating HIV vaccine strategies. The extreme resistance to neutralizing antibody (NAb) many commonly used strains, such as SIVmac251/239 and SIVsmE543-3, limits their potential relevance the role NAb in protection. In contrast, SIVsmE660 is uncloned that appears be more sensitive antibody. To evaluate this model, we generated full-length neutralization-sensitive molecular clones...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of disease 19 (COVID-19) and employs angiotensin-converting enzyme (ACE2) as receptor. Although expression ACE2 crucial for cellular entry, we found that interaction between Spike (S) protein in same cells led to its downregulation through degradation lysosomal compartment via endocytic pathway. Interestingly, ability S from previous variants concern (VOCs) downregulate was variant-dependent correlated with...
To assess the molecular epidemiology of HIV-1 in Republic Congo (Congo), we investigated 29 HIV-1s obtained from 82 Congolese AIDS and ARC patients 1996 1997. Part env region including V3 loop was phylogenetically analyzed. The genotypes observed were varied: specimens, 12 (41%) subtype A, 1 (3%) D, 6 (21%) G, H, 2 (7%) J, could not be classified as any known subtypes (U, unclassified). heterogeneous profile HIV1 infection different profiles neighboring Central African countries. These data...
Inducing neutralizing antibodies (NAb) is the key to developing a protective vaccine against human immunodeficiency virus type 1 (HIV-1). To clarify neutralization mechanism of simian (SIV), we analyzed NAb B404, which showed potent and broad activity various SIV strains. In 4 SIVsmH635FC-infected macaques, B404-like using specific VH3 gene with long complementarity-determining region 3 loop λ light chain were major NAbs in terms number potency. This biased induction was observed all...
Two simian immunodeficiency virus strain mac (SIVmac)/human type 1(HIV-1) chimeric viruses (SHIVs), designated NM-3 and NM-3n, with env derived from HIV-1 defective vpr (plus nef for NM-3), were inoculated into seven macaques. These macaques transiently or persistently infected most of them produced long-lasting neutralizing antibodies Env-specific killer T cells to no AIDS-like symptoms. When they challenged another SHIV intact (designated NM-3rN), all protected as judged by recovery, DNA...
ABSTRACT A minor fraction of simian immunodeficiency virus (SIV)-infected macaques progress rapidly to AIDS in the absence SIV-specific immune responses. Common mutations conserved residues env three SIVsmE543-3-infected rapid-progressor (RP) suggest evolution a common viral variant RP macaques. The goal present study was analyze biological properties these variants vitro and vivo through derivation infectious molecular clones. Virus isolated from macaque, H445 used inoculate six naive...
The humoral immune response is a mechanism that potently suppresses or prevents viral infections. However, genetic diversity and resistance to antibody-mediated neutralization are serious obstacles in controlling HIV-1 infection. In this study, we isolated monoclonal antibodies from an SIV-infected macaque by using the phage display method characterize SIV Variable regions of immunoglobulin genes were amplified rhesus macaque-specific primers inserted into phagemid pComb3X, which produced...
Neutralizing potency of humoral immune responses induced by prior infection or vaccination is vital for protecting individuals and population against severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). However, the emergence viral variants that can evade neutralization vaccine- infection-induced immunity a significant public health threat requires continuous monitoring. Here, we have developed novel scalable chemiluminescence-based assay assessing SARS-CoV-2-induced...
We quantified a population of recombinants in natural vitro infection, using wild-type viruses without any pressure. It was found that emerged early after infection and constituted more than 20% the whole proviral 15 days infection. Furthermore, were isolated as infectious by simple limiting dilution. These results imply that, addition to high mutation rate human immunodeficiency virus type 1 (HIV-1), recombination among HIV-1 strains plays significant part development diversity HIV-1.
To investigate the role of apoptosis in progressive loss CD4+ lymphocytes HIV infection, we have used macaques infected with SHIV, a hybrid virus and simian immunodeficiency (SIV). In present study, sequentially analyzed induction acute phase SHIV infection. Four pathogenic SHIV89.6P, four nonpathogenic NM-3rN, were during first 2 or 4 weeks postinfection. 89.6P-infected number peripheral cells sharply decreased at postinfection was maintained below 50/mul until postinfection, while...
ABSTRACT Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants the attenuated poxvirus modified vaccinia Ankara (MVA) provided protection from high viremia AIDS following challenge a pathogenic strain SIV. Although all animals became infected, plasma was significantly reduced in received MVA-SIV recombinant vaccines compared nonrecombinant MVA. Most importantly, reduction resulted significant increase median...
The CD4-induced (CD4i) epitopes in gp120 includes the co-receptor binding site, which are formed and exposed after interaction with CD4. Monoclonal antibodies (mAbs) to CD4i exhibit limited neutralizing activity because of restricted access their epitopes. However, small fragment counterparts such as single-chain variable fragments (scFvs) have been reported neutralize a broad range viruses compared full-size IgG molecule. To identify epitope site responsible for this neutralization we...
Objective: To examine the biological properties of HIV-1/SIVmac chimeric viruses from HIV-1 isolates that have different replication rates, cell tropisms and cytopathicities. Design methods: Four with gag, pol, vif, vpx, nef long terminal repeats SIVmac vpr, tat, rev, vpu env various were constructed compared in vitro. Cynomolgus monkeys inoculated two chimeras replicative monkey peripheral blood mononuclear cells (PBMC). Results: The type-specific neutralization by monoclonal antibodies...
To clarify the physiological function of two zinc finger motifs in nucleocapsid (NC) domain Gag protein human immunodeficiency virus type 1 (HIV-1), we changed cysteine to serine either or both by site-directed mutagenesis. Viral infectivity was lost any mutations, but their effects appeared differently respective mutants. Northern blot analysis showed that first mutant far less efficient (approximately 10% wild type) genomic RNA encapsidation and dual fingers completely failed encapsidate...
The use of HIV-1env/SIVmacchimeric viruses expressing divergent HIV-1 envelopes clinical isolates, facilitates homologous and heterologous evaluation various recombinant envelope vaccine candidates in lower primates. In this study we compare thein vitroandin vivoinfectivity, via intravenous (IV) intravaginal (IVAG) routes infection, stocks chimeric expressingenvfrom four different clade B isolates. TCID50/ml was 7.1 × 104, 1.0 6.3 1.2 103for SHIVsf13, SHIVHan2, SHIVNM-3rn, SHIVW6.1D,...