A5063373826- Virology and Viral Diseases
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Inflammasome and immune disorders
- HIV Research and Treatment
- interferon and immune responses
- Immune Response and Inflammation
- Virus-based gene therapy research
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- Yersinia bacterium, plague, ectoparasites research
- Gout, Hyperuricemia, Uric Acid
- Cytomegalovirus and herpesvirus research
- Immunodeficiency and Autoimmune Disorders
- Trace Elements in Health
- Gut microbiota and health
- Tryptophan and brain disorders
- Toxoplasma gondii Research Studies
- Frailty in Older Adults
- Malaria Research and Control
- Calcium signaling and nucleotide metabolism
- Sepsis Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Cancer Research and Treatments
Tufts University
2020-2024
Beth Israel Deaconess Medical Center
2016-2018
Harvard University
2018
Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of safe effective ZIKV vaccine therefore an urgent global health priority. Here we demonstrate that three different platforms protect against challenge rhesus monkeys. A purified inactivated induced ZIKV-specific neutralizing antibodies completely protected monkeys strains from both Brazil Puerto Rico. Purified immunoglobulin vaccinated also...
Significance While ZBP1 is well documented to drive cell death in response viruses, its role the context of Toll-like receptor (TLR)–mediated immune activation remains less defined. Here, we show that promotes inflammation bacterial lipopolysaccharide (LPS) or double-stranded RNA (dsRNA). In a dose dependent manner, recruitment RIPK1 TLR3/4 adaptor TRIF, activating downstream inflammatory signaling. plays crucial TRIF-dependent responses vivo , as Zbp1 −/− mice exhibited resistance...
Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika (ZIKV), promoting increased ZIKV infection vitro. However, the correlation between vitro and vivo findings is not well characterized. Thus, we evaluated impact heterotypic flavivirus immunity on titers biofluids rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever were compared to flavivirus-naïve animals following a Brazilian strain. Sera from...
Not all vaccines afford robust protection against ZIKV challenge in rhesus monkeys at 1 year after vaccination.
Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1β (IL-1β) release occurs through caspase-1 caspase-11-mediated gasdermin D pore formation. In vivo, lipopolysaccharide (LPS) result in IL-1β secretion. vitro, however, murine macrophages require a second "danger signal" for the inflammasome-driven maturation of IL-1β. Recent reports have shown caspase-8-mediated pyroptosis LPS-activated but provided conflicting evidence...
Despite the existing association of gut dysbiosis and T cell inflammation in heart failure (HF), whether how microbes contribute to immune responses, cardiac fibrosis dysfunction HF remains largely unexplored. Our objective was investigate is induced by pressure overload, its effect activation, adverse remodeling, dysfunction.We used 16S rRNA sequencing fecal samples discovered that overload-induced transverse aortic constriction (TAC) results dysbiosis, characterized a reduction tryptophan...
TNF mediates a variety of biological processes including cellular proliferation, inflammatory responses, and cell death is therefore associated with numerous pathologies autoinflammatory diseases septic shock. The responses to have been studied extensively downstream TNF-R1 are believed rely on the formation proinflammatory complex I prodeath II, respectively. We recently identified similar multimeric TLR4, termed TRIFosome, that regulates inflammation in response LPS or Yersinia...
ABSTRACT Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common such as Ad5. However, baseline immunity these still exists in human populations. Traditional cloning of new vaccine is a long cumbersome process that takes 2 months or more requires rare unique restriction enzyme sites. Here we describe novel, enzyme-independent method for rapid reduces the total procedure 1 week. We 14 novel from rhesus monkeys can be grown high titers...
In vivo clonal expansion of HIV-infected T cells is an important mechanism viral persistence. some cases, driven by HIV proviral DNA integrated into one a handful genes. To investigate this phenomenon in vitro, we infected primary CD4+ with construct expressing GFP and, after nearly 2 mo culture and multiple rounds activation, analyzed the resulting integration site distribution. each three replicates from two donors, detected large clusters sites breakpoints, implying selection. These all...
Signaling through classical death receptor Fas was mainly appreciated as a pro-death pathway until recent reports characterized pro-inflammatory outcomes of Fas-mediated activation in pathological contexts. How signaling can switch to is poorly understood. Herein, we report that macrophages and neutrophils, the Toll-like (TLR) adapter CD14 determines inflammatory output signaling. Our findings propose crucial chaperone internalization resulting Cd14
Caspase-8-dependent pyroptosis has been shown to mediate host protection from Yersinia infection. For this mode of cell death, the kinase activity receptor-interacting protein 1 (RIPK1) is required, but autophosphorylation sites required drive caspase-8 activation have not determined. Here, we show that non-canonical RIPK1 at threonine 169 (T169) necessary for caspase-8-mediated pyroptosis. Mice with alanine in T169 position are highly susceptible dissemination. Mechanistically, delayed...