A5071355476- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- HIV Research and Treatment
- Parvovirus B19 Infection Studies
- Viral Infections and Immunology Research
- Virus-based gene therapy research
- HIV/AIDS Research and Interventions
- Animal Disease Management and Epidemiology
- Toxoplasma gondii Research Studies
- Virology and Viral Diseases
- HIV/AIDS drug development and treatment
- Animal Virus Infections Studies
- Mosquito-borne diseases and control
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Viral-associated cancers and disorders
- Plant Virus Research Studies
- Antimicrobial Resistance in Staphylococcus
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Outbreaks Research
- Epigenetics and DNA Methylation
- Orthopedic Infections and Treatments
- T-cell and Retrovirus Studies
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
University of California, Davis
2011-2025
Pfizer (United States)
2022
National Center for Infectious Diseases
2019
Oregon National Primate Research Center
2006
Duke Medical Center
2005
Paul Ehrlich Institut
1965-1974
Max Planck Institute of Psychiatry
1966
Simple affordable interventions are needed to reduce vertical human immunodeficiency virus (HIV) transmission in developing countries. The efficacy of 2 low doses (4 mg/kg, subcutaneously) or 1 high dose (30 the reverse-transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) protect newborn macaques against simian (SIV) infection was investigated. Thirteen were inoculated orally with virulent SIVmac251. 4 placebo-treated animals (group A) became persistently infected....
An infant macaque model was developed to test pediatric vaccine candidates aimed at reducing HIV transmission through breast-feeding. Infant macaques were given multiple immunizations during the first 3 weeks of life with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins Gag, Pol, and Env (ALVAC-SIV or modified vaccinia Ankara [MVA]-SIV). After repeated daily oral inoculations virulent SIVmac251 4 age, significantly fewer ALVAC-SIV-immunized...
Congenital cytomegalovirus (cCMV) is the leading infectious cause of neonatal neurological impairment worldwide, but viral factors enabling vertical spread across placenta remain undetermined. The pentameric complex (PC), composed subunits gH/gL/UL128/UL130/UL131A, has been demonstrated to be important for entry into nonfibroblast cells in vitro. These findings link PC broad cell tropism and virus dissemination vivo, denoting all as potential targets intervention strategies vaccine...
Implicit with the use of animal models to test human cytomegalovirus (HCMV) vaccines is assumption that viral challenge vaccinated animals reflects anticipated virus-host interactions following exposure humans HCMV. Variables vaccine studies include route and titer virus, as well genomic coding content virus. This study was initiated provide a better context for conducting trials nonhuman primates by determining whether in vivo phenotype culture-passaged strains rhesus (RhCMV) comparable...
Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, rodent models. Although RNA extracted from milk has been used to assay the transcriptome non-invasively, this not adequately validated in primates. Thus, objectives current study were assess suitability lactating rhesus macaques as a model for humans determine whether fractions is representative tissue purpose studying milk-producing cells. We confirmed that macaque...
ABSTRACT A vaccine to protect human immunodeficiency virus (HIV)-exposed infants is an important goal in the global fight against HIV pandemic. Two major challenges pediatric design are competence of neonatal/infant immune system comparison adult and frequent exposure via breast-feeding. Based on hypothesis that effective needs elicit antiviral responses directly at site entry, pattern dissemination relation host was determined mucosal lymphoid tissues infant macaques 1 week after multiple...
The use of animal models human cytomegalovirus (HCMV) infection is critical to refine HCMV vaccine candidates. Previous reports have demonstrated that immunization rhesus monkeys against (RhCMV) can reduce both local and systemic replication RhCMV following experimental challenge. These studies used prime/boost combinations DNA expression plasmids alone or priming boosting with either inactivated virion particles modified vaccinia virus Ankara (MVA) expressing the same antigens. Viral...
Cytomegaloviruses (CMVs) are highly adapted to their host species resulting in strict specificity. Hence, vivo examination of all aspects CMV biology employs animal models using host-specific CMVs. Infection rhesus macaques (RM) with (RhCMV) has been established as a representative model for infection humans HCMV due the close evolutionary relationships both and virus. However, only available RhCMV clone that permits genetic modifications is based on 68–1 strain which passaged fibroblasts...
Cytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV during pregnancy leads to a higher frequency (cCMV) than maternal re-infection, suggesting that immunity confers partial protection. However, poorly understood immune correlates protection against placental transmission contributes current lack an approved vaccine prevent cCMV. In this study, we characterized kinetics plasma rhesus (RhCMV) viral load (VL) RhCMV-specific antibody...
Rhesus cytomegalovirus–based (RhCMV-based) vaccine vectors induce immune responses that protect ~60% of rhesus macaques (RMs) from SIVmac239 challenge. This efficacy depends on induction effector memory–based (EM-biased) CD8+ T cells recognizing SIV peptides presented by major histocompatibility complex-E (MHC-E) instead MHC-Ia. The phenotype, durability, and RhCMV/SIV-elicited cellular were maintained when vector spread was severely reduced deleting the antihost intrinsic immunity factor...
Summary: Previous studies have demonstrated that tenofovir (9-[2-(phosphonomethoxy)propyl]adenine; PMPA) treatment is usually very effective in suppressing viremia macaques infected with simian immunodeficiency virus (SIV). The present study focuses on a subset of infant were chronically highly virulent SIVmac251, and for which prolonged failed to significantly suppress viral RNA levels plasma despite the presence tenofovirsusceptible at onset therapy. While untreated animals similarly high...
Abstract: Kaposi's sarcoma‐associated herpesvirus (KSHV) is a γ ‐herpesvirus associated with sarcoma (KS) and two lymphoproliferative diseases, primary effusion lymphoma (PEL) multicentric Castleman's disease. Studies on the biology pathogenesis of KSHV have been limited by lack efficient cell culture systems suitable animal model for KS. Here we report experimental inoculation SIV‐positive SIV‐negative rhesus macaques KSHV‐infected PEL cells or preparations derived from cells. Low levels...
Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model to determine whether topical (oral) administration antiviral compounds the nursing could reduce human transmission through breast-feeding. The reverse-transcriptase inhibitor tenofovir was selected because previous demonstrations that systemic drug levels are effective in preventing SIV infection. To mimic multiple exposures during breast-feeding, 14 were fed 15 low doses SIVmac251 without chemical...
Mucosal transmission is the predominant mode of human immunodeficiency virus (HIV) infection worldwide, and mucosal innate interferon response represents an important component earliest host to infection. Our goal here was assess changes in mRNA expression genes after oral simian (SIV) inoculation rhesus macaques (Macaca mulatta) that were followed throughout their course disease progression. The SIV plasma viral load highest macaque progressed rapidly AIDS (99 days) lowest more slowly (>700...
Abstract The development of a vaccine to prevent congenital human cytomegalovirus (HCMV) disease is public health priority. We tested rhesus CMV (RhCMV) prototypes HCMV candidates in seronegative macaque oral challenge model. Immunogens included recombinant pentameric complex (PC; gH/gL/pUL128/pUL130/pUL131A), postfusion gB ectodomain, and DNA plasmid that encodes pp65-2. Immunization with QS21-adjuvanted PC alone or the other immunogens elicited neutralizing titers comparable those by RhCMV...
ABSTRACT There is accumulating evidence that the viral interleukin-10 (vIL-10) ortholog of both human and rhesus cytomegalovirus (HCMV RhCMV, respectively) suppresses functionality cell types are critical to contain virus dissemination help shape long-term immunity during earliest virus-host interactions. In particular, exposure macrophages, peripheral blood mononuclear cells, monocyte-derived dendritic plasmacytoid cells vIL-10 multiple effector functions including, notably, those link...
Significance Cytomegalovirus (CMV) is a herpesvirus that causes severe disease in infants and immunocompromised people. Development of vaccine to control the spread CMV has been decades-long goal. Most strategies target glycoprotein B (gB), viral used for entry into host cells. We have instead targeted interleukin-10 (vIL-10), an immunomodulatory protein. investigated whether these two approaches combined are capable controlling horizontal transmission nonhuman primate model. Our results...
Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neonatal neurological impairment but essential virological determinants transplacental CMV transmission remain unclear. The pentameric complex (PC), composed five subunits, glycoproteins H (gH), gL, UL128, UL130, and UL131A, for efficient entry into non-fibroblast cells in vitro . Based on this role cell tropism, PC considered a possible target vaccines immunotherapies to prevent cCMV. To determine non-human...
Rhesus cytomegalovirus (RhCMV) infection of rhesus macaques (Macaca mulatta) is a valuable nonhuman primate model human CMV (HCMV) persistence and pathogenesis. In vivo studies predominantly use tissue culture-adapted variants RhCMV that contain multiple genetic mutations compared to wild-type (WT) RhCMV. many studies, animals have been inoculated by nonnatural routes (e.g., subcutaneous, intravenous) do not recapitulate disease progression via the normative route mucosal exposure....