A5088402507- Mosquito-borne diseases and control
- Virology and Viral Diseases
- Viral Infections and Vectors
- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- SARS-CoV-2 detection and testing
- SARS-CoV-2 and COVID-19 Research
- Insect symbiosis and bacterial influences
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Animal Virus Infections Studies
- Global Maternal and Child Health
- Viral gastroenteritis research and epidemiology
- Biosensors and Analytical Detection
- Folate and B Vitamins Research
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Transplantation: Methods and Outcomes
- interferon and immune responses
- HIV-related health complications and treatments
- COVID-19 Impact on Reproduction
- Wildlife Ecology and Conservation
- Poxvirus research and outbreaks
University of Wisconsin–Madison
2016-2025
Universidad Nacional de Asunción
2010-2023
Madison Group (United States)
2019-2023
Centro Universitário Una
2010-2017
International AIDS Vaccine Initiative
2006-2011
National Institutes of Health
2003-2005
National Human Genome Research Institute
2003-2005
Abstract Infection with Asian-lineage Zika virus (ZIKV) has been associated Guillain–Barré syndrome and fetal abnormalities, but the underlying mechanisms remain poorly understood. Animal models of infection are thus urgently needed. Here we show that rhesus macaques susceptible to by an ZIKV closely related strains currently circulating in Americas. Following subcutaneous inoculation, RNA is detected plasma 1 day post (d.p.i.) all animals ( N =8, including 2 pregnant animals), also present...
Infection with Zika virus (ZIKV) is associated human congenital fetal anomalies. To model outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals a previous study contemporary the current report clear viremia within 10–12 days, maternal was prolonged 3 of 4 pregnancies. Fetal head growth velocity last month gestation determined by ultrasound assessment circumference decreased comparison biparietal diameter...
The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within between individual hosts. Using domestic cats as a model, we show that consensus sequences remain largely unchanged over time hosts, while dynamic sub-consensus diversity reveals processes of drift weak purifying selection. We further identify notable variant at amino acid position 655 in Spike...
An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) and challenged with highly pathogenic heterologous isolate. Vaccinees reduced viral replication by ∼2 logs between weeks 2–32 (P ≤ 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated control completely suppressed acute phase the challenge virus,...
Background Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome adults and congenital birth defects including microcephaly developing fetus. Because development vaccine is top research priority genetic antigenic variability many RNA viruses limits effectiveness vaccines,...
Abstract Mouse and nonhuman primate models now serve as useful platforms to study Zika virus (ZIKV) pathogenesis, candidate therapies, vaccines, but they rely on needle inoculation of virus: the effects mosquito-borne infection disease outcome have not been explored in these models. Here we show that via mosquito bite delays ZIKV replication peak viral loads rhesus macaques. Importantly, mosquito-infected animals tissue distribution was limited hemolymphatic tissues, female reproductive...
Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with Puerto Rican ZIKV isolate in the first trimester. The was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial demise 49 days post (gestational day 95). Significant pathology at maternal-fetal interface included acute chorioamnionitis, placental infarcts, leukocytoclastic vasculitis myometrial radial arteries. RNA disseminated...
Congenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak in 2015/2016. It has been proposed that mutations unique Asian/American-genotype explain, at least part, ability of Asian/American ZIKV cause congenital syndrome (CZS). Recent studies identified infecting humans arose coincident with French Polynesia and were stably maintained subsequent spread Americas. Here we show African can infect harm fetuses S139N substitution associated is not...
Zika virus (ZIKV) is a mosquito-borne originally discovered in captive monkey living the Forest of Uganda, Africa, 1947. Recently, an outbreak South America has shown that ZIKV infection can cause myriad health effects, including birth defects children women infected during pregnancy. Here, we sought to investigate wild African primates better understand its emergence and spread, looking for evidence active or prior infection. Our results suggest up 16% some populations nonhuman primate...
Zika virus (ZIKV) and dengue (DENV) are genetically antigenically related flaviviruses that now co-circulate in much of the tropical subtropical world. The rapid emergence ZIKV Americas 2015 2016, its recent associations with Guillain-Barré syndrome, birth defects, fetal loss have led to hypothesis DENV infection induces cross-reactive antibodies influence severity secondary infections. It has also been proposed pre-existing immunity could affect pathogenesis. We examined outcomes infections...
It has recently been shown that polymorphism at the rhesus macaque TRIM5 locus can affect simian immunodeficiency virus (SIV) replication. Here we show alleles also acquisition of SIVsmE660. Animals coexpressing TRIM5(TFP) and TRIM5(CypA) took significantly longer to become infected with SIVsmE660, but not SIVmac239, after repeated limiting-dose intrarectal challenge than did animals expressing other allele combinations. Our results indicate be a barrier productive infection this should...
Developing biological interventions to control human immunodeficiency virus (HIV) replication in the absence of antiretroviral therapy (ART) could contribute development a functional cure. As potential alternative ART, interleukin-15 (IL-15) superagonist ALT-803 has been shown boost number and function HIV-specific CD8+ T NK cell populations vitro Four simian (SIV)-positive rhesus macaques, three whom possessed major histocompatibility complex alleles associated with SIV all had received...
Zika virus is present in urine, saliva, tears, and breast milk, but the transmission risk associated with these body fluids currently unknown. Here we evaluate of through mucosal contact rhesus macaques. Application high-dose directly to tonsils three macaques results detectable plasma viremia all animals by 2 days post-exposure; replication kinetics are similar those observed infected subcutaneously. Three additional inoculated subcutaneously served as saliva donors assess from oral...
Abstract Evidence-based public health approaches that minimize the introduction and spread of new SARS-CoV-2 transmission clusters are urgently needed in United States other countries struggling with expanding epidemics. Here we analyze 247 full-genome sequences from two nearby communities Wisconsin, USA, find surprisingly distinct patterns viral spread. Dane County had 12 th known States, but this did not lead to descendant community Instead, outbreak was seeded by multiple later...
SARS-CoV-2 testing is crucial to controlling the spread of this virus, yet shortages nucleic acid extraction supplies and other key reagents have hindered response COVID-19 in US. Several groups described loop-mediated isothermal amplification (LAMP) assays for SARS-CoV-2, including directly from nasopharyngeal swabs eliminating need short supply. Frequent surveillance individuals attending work or school currently unavailable most people but will likely be necessary reduce ~50% transmission...
In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about impacts gestational African-lineage infections. Given high human immunodeficiency (HIV) burdens regions where circulates, we evaluated whether pregnant rhesus macaques simian (SIV) have higher ZIKV-associated defects. Remarkably, both SIV+ and SIV- animals, infection early first trimester caused...
An effective human immunodeficiency virus (HIV) vaccine will likely need to reduce mucosal transmission and, if infection occurs, control replication. To determine whether our best simian (SIV) can achieve these lofty goals, we vaccinated eight Indian rhesus macaques with SIVmac239Delta nef and challenged them intrarectally (i.r.) repeated low doses of the pathogenic heterologous swarm isolate SIVsmE660. We detected a significant reduction in acquisition SIVsmE660 comparison that for naïve...
Studies of influenza transmission are necessary to predict the pandemic potential emerging viruses. Currently, both ferrets and guinea pigs used in such studies, but these species distantly related humans. Nonhuman primates (NHP) share a close phylogenetic relationship with humans may provide an enhanced means model virological immunological events virus transmission. Here, for first time, it was demonstrated that human isolate can productively infect be transmitted between common marmosets...
Key biological properties such as high genetic diversity and evolutionary rate enhance the potential of certain RNA viruses to adapt emerge. Identifying with these in their natural hosts could dramatically improve disease forecasting surveillance. Recently, we discovered two novel members viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) Kibale National Park, Uganda. Nearly nothing is...
Defining the complex dynamics of Zika virus (ZIKV) infection in pregnancy and during transmission between vertebrate hosts mosquito vectors is critical for a thorough understanding viral transmission, pathogenesis, immune evasion, potential reservoir establishment. Within-host diversity ZIKV low, which makes it difficult to evaluate dynamics. To overcome this biological hurdle, we constructed molecularly barcoded ZIKV. This stock consists "synthetic swarm" whose members are genetically...
ZIKV was first identified in 1947 Africa, but most of our knowledge is based on studies the distinct Asian genetic lineage, which caused outbreak Americas 2015 to 2016. In its recent update, WHO stated that improved understanding African-lineage pathogenesis during pregnancy must be a priority.
Effector function is not required for a potent HIV envelope–specific broadly neutralizing antibody to protect nonhuman primates from SHIV infection.
Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether activities are sufficient for protection is unclear. We previously identified an variable 2 (V2) apex of Env trimer (PGT145) that potently directs lysis SIV-infected cells by NK poorly neutralizes SIV infectivity. To determine if ADCC protection, separate groups six rhesus macaques were treated with PGT145 or a control (DEN3)...
Abstract Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting fetal harm IIb MPXV, that is currently circulating Western Hemisphere, remains unknown. We established a rhesus macaque model of MPXV early gestation inoculation. Three pregnant macaques were inoculated intradermally 1.5 × 10^5 plaque forming units (PFU) near gestational day (GD) 30 and animals monitored viremia maternal well-being. Animals euthanized...