A5027442064- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Malaria Research and Control
- Viral Infections and Outbreaks Research
- COVID-19 epidemiological studies
- Influenza Virus Research Studies
- HIV Research and Treatment
- Virology and Viral Diseases
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Insect symbiosis and bacterial influences
- Dengue and Mosquito Control Research
- Infectious Encephalopathies and Encephalitis
- Zoonotic diseases and public health
- Virus-based gene therapy research
- Vector-borne infectious diseases
- Global Maternal and Child Health
- COVID-19 Clinical Research Studies
- Vibrio bacteria research studies
- vaccines and immunoinformatics approaches
- Research on Leishmaniasis Studies
- Pneumonia and Respiratory Infections
- Plant Virus Research Studies
- Cytomegalovirus and herpesvirus research
University of California, Berkeley
2016-2025
Berkeley College
2011-2023
Berkeley Public Health Division
1999-2022
Columbia University Irving Medical Center
2022
Sustainable Sciences Institute
2005-2021
Universidad Nacional
2021
University of Arizona
2021
Clinica de Salud del Valle de Salinas
2021
London School of Hygiene & Tropical Medicine
2021
Innovative Genomics Institute
2021
For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown enhance viral replication in vitro and severe disease animal models. Although suspected, such antibody-dependent enhancement not occur humans. Using multiple statistical approaches study long-term pediatric cohort Nicaragua, we show that risk is highest within narrow preexisting anti-DENV titers. By contrast, observe protection from all symptomatic at high Thus, immune correlates must be evaluated...
Characterizing the Zika virus antibody response Given public health emergency that poses, scientists are seeking to understand Zika-specific immune response. Stettler et al. analyzed 119 monoclonal antibodies isolated from four donors were infected with during present epidemic, including two individuals had previously been dengue virus, another member of flavivirus family. Neutralizing primarily recognized envelope protein domain III (EDIII) or quaternary epitopes on intact and an...
The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up ~100 million cases of annually worldwide. Severe disease is thought result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells together induce vasoactive cytokines, causing vascular leakage leads shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results leakage. DENV nonstructural protein 1 (NS1)...
Abstract Over the past two decades, dengue virus serotype 3 (DENV-3) has caused unexpected epidemics of hemorrhagic fever (DHF) in Sri Lanka, East Africa, and Latin America. We used a phylogenetic approach to evaluate roles evolution transport emergence these outbreaks. Isolates from geographically distant are closely related belong DENV-3, subtype III, which originated Indian subcontinent. The DHF Lanka 1989 correlated with appearance there new III variant. This variant likely spread...
Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate myeloid cells vitro by promoting entry via Fcgamma receptors (FcgammaR), a process known as antibody-dependent enhancement (ADE). However, despite decades investigation, no vivo model for antibody has been described. Analogous human infants who receive anti-DV transplacental transfer and develop...
The global spread of dengue virus (DENV) infections has increased viral genetic diversity, some which appears associated with greater epidemic potential. mechanisms governing fitness in epidemiological settings, however, remain poorly defined. We identified a determinant foreign dominant (PR-2B) DENV serotype 2 (DENV-2) clade, emerged during the 1994 Puerto Rico and replaced an endemic (PR-1) DENV-2 clade. PR-2B produced levels subgenomic flavivirus RNA (sfRNA) relative to genomic...
To investigate age-related differences in dengue severity, 114 infants, 1,211 children, and 346 adults with laboratory-confirmed virus (DEN) infections presenting to three hospitals major urban centers Nicaragua were recruited from 1999 2001. The age distribution of cases the circulating serotype (predominantly DEN2) representative national data. Similar results obtained when either hemorrhagic fever/dengue shock syndrome or its principal manifestations (vascular permeability, internal...
Lack of an appropriate animal model for dengue virus (DEN), which causes fever and hemorrhagic fever/dengue shock syndrome (DHF/DSS), has impeded characterization the mechanisms underlying disease pathogenesis. The cardinal feature DHF/DSS, severe form DEN infection, is increased vascular permeability. To develop a murine that more relevant to novel strain, D2S10, was generated by alternately passaging non-mouse-adapted strain between mosquito cells mice, thereby mimicking natural...
Zika virus (ZIKV), chikungunya (CHIKV), and dengue (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia clinical presentation of patients infected with 1 or more these viruses. Acute-phase serum samples from 346 a suspected arboviral illness were tested using multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, DENV. Viremia was quantitated each detected virus, information request forms submitted sample recorded. A total...
Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide. Systemic plasma leakage, leading to hypovolemic shock potentially fatal complications, critical determinant of dengue severity. Recently, we others described novel pathogenic effect secreted virus (DENV) non-structural protein 1 (NS1) triggering hyperpermeability human endothelial cells vitro systemic vascular leakage vivo. NS1 was shown activate toll-like receptor 4 signaling primary...
The rapid spread of dengue is a worldwide public health problem. In two clinical studies in Managua, Nicaragua, we observed an abrupt increase disease severity across several epidemic seasons virus serotype 2 (DENV-2) transmission. Waning DENV-1 immunity appeared to the risk severe subsequent DENV-2 infections after period cross-protection. coincided with replacement Asian/American NI-1 clade new clade, NI-2B. vitro analyses viral isolates from clades and analysis viremia patient blood...
Flaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved viral replication, immune evasion, and vascular leakage during dengue virus infection. However, the contribution of NS1 from related flaviviruses to pathogenesis remains unknown. Here, we demonstrate that dengue, Zika, West Nile, Japanese encephalitis, yellow fever viruses selectively binds alters permeability human endothelial cells...
We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection animal cells. Small RNA-based mechanisms such as interference (RNAi) been shown plant and invertebrate systems play a key role host responses infection. Although homologs of the RNAi effector pathways are present mammalian cells, can launch an RNAi-mediated degradation experimentally targeted mRNAs, any for host-virus interactions remains be characterized....
Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Fever severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants inapparent versus symptomatic infection outcome. Here, we analyzed over 2,000 2004 2011 in prospective pediatric cohort study Managua, Nicaragua. Symptomatic...
The clinical outcomes associated with Zika virus (ZIKV) in the Americas have been well documented, but other aspects of pandemic, such as attack rates and risk factors, are poorly understood. We prospectively followed a cohort 1453 urban residents Salvador, Brazil, and, using an assay that measured immunoglobulin G3 (IgG3) responses against ZIKV NS1 antigen, we estimated 73% individuals were infected during 2015 outbreak. Attack spatially heterogeneous, varying by factor 3 within community...
CD4+ cytotoxic T lymphocytes (CD4-CTLs) have been reported to play a protective role in several viral infections. However, little is known humans about the biology of CD4-CTL generation, their functional properties, and heterogeneity, especially relation other well-described memory cell subsets. We performed single-cell RNA sequencing more than 9000 cells unravel transcriptional profile, clonality humans. Single-cell differential gene expression analysis revealed spectrum transcripts,...
Epidemiologic studies indicate that obesity increases the risk of severe complications and death from influenza virus infections, especially in elderly individuals. This work investigates effect on duration viral shedding within household transmission Managua, Nicaragua, over 3 seasons (2015–2017). Symptomatic obese adults were shown to shed A 42% longer than nonobese (adjusted event time ratio [ETR], 1.42; 95% confidence interval [CI], 1.06–1.89); no association was observed with B...