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Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus.

There is a need to develop a highly effective vaccine against the emerging chikungunya virus (CHIKV), a mosquito-borne Alphavirus that cause … We review the characterization of innate and adaptive immune responses induced in mice and nonhuman primates by the MVA-CHIKV vaccine candidate and examine its efficacy in animal models, with promising preclinical findings needed prior to the approval of human clinical trials.

Advancing our understanding of HIV co-infections and neurological disease using the humanized mouse.

Humanized mice have become an important workhorse model for HIV research. Advances that enabled development of a human immune system in immune deficient mouse strains have aided new basic research in HIV pathogenesis and immune dysfunction. The small animal features facilitate development of clinical interventions that are difficult to study in clinical cohorts, and avoid the high cost and regulatory burdens of using non-human primates. The model also overcomes the host restriction of HIV for human immune cells which limits discovery and translational research related to important co-infection…

Shigella ubiquitin ligase IpaH7.8 targets gasdermin D for degradation to prevent pyroptosis and enable infection.

The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show that the Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor of GSDMD. Shigella is an enteroinvasive bacterium that causes hemorrhagic gastroenteritis in primates, but not rodents. IpaH7.8 contributes to species specificity by ubiquitinating human, but not mouse, GSDMD and targeting it for proteasomal degradation. Accordingly, infection of human epithe…

Genotyping of Toxoplasma gondii in a lethal toxoplasmosis outbreak affecting captive howler monkeys (Alouatta sp.).

BACKGROUND: Toxoplasmosis is a zoonotic disease that affects humans and warm-blooded animals. This study describes an outbreak of toxoplasmo … n all howler monkeys. CONCLUSIONS: Our results support the notion that some species of neotropical primates are highly susceptible to toxoplasmosis and the hypothesis that capuchins (S. apella) may be resistant.

Neural mechanisms of aggression across species.

Aggression is a social behavior essential for securing resources and defending oneself and family. Thanks to its indispensable function in c … of aggression and the relevant neural substrates across species, highlighting findings in rodents, primates and songbirds.

Safety and immunogenicity of 17DD attenuated yellow fever vaccine in howler monkeys (Alouatta spp.).

BACKGROUND: Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP). METHODS: Susceptible howler monkeys were immunized with three different concentrations of the human Brazilian commercial YF17DD vaccine. Post-vaccination viremia/RNAemia, immunogenicity, and safety were characterized. RESULTS: The vaccine did not produce YF clinical manifestations in any of the NHPs. After immunization, all animal…

Establishment of an osteoporosis model in tree shrews by bilateral ovariectomy and comprehensive evaluation.

Osteoporosis (OP) treatment has always been challenging for elderly menopausal females. An animal model with a closer genetic association to human OP is essential for treatment research. Given its close genetic association to primates, the tree shrew is a suitable candidate for meeting the requirements for such an animal model. In the present study, a tree shrew OP model induced by ovariectomy (OVX), was established. Evaluation by multiple analysis methods, including blood biochemical indicators, uterus coefficients, micro-computed tomography analysis, histochemical analysis and scanning elect…

Structure of the yellow fever NS5 protein reveals conserved drug targets shared among flaviviruses.

Yellow fever virus (YFV) is responsible for devastating outbreaks of Yellow fever (YF) in humans and is associated with high mortality rates. Recent large epidemics and epizootics and exponential increases in the numbers of YF cases in humans and non-human primates highlight the increasing threat YFV poses, despite the availability of an effective YFV vaccine. YFV is the first human virus discovered, but the structures of several of the viral proteins remain poorly understood. Here we report the structure of the full-length NS5 protein, a key enzyme for the replication of flaviviruses that con…

Аденовирусные векторы в гематопоэтическом редактировании генома стволовых клеток.

Редактирование генома гематополиетических стволовых клеток (HSC) представляет собой терапевтический вариант для ряда гематологических генетических заболеваний, поскольку ГПСЦ обладают потенциалом для самовосстановления и дифференциации по всем линиям кровеносных клеток. В настоящем обзоре представлены достижения в области редактирования генома в HSC с использованием аденовирусных векторов в качестве средств доставки. Мы сосредоточимся на модифицированных аденовирусных векторах, находящихся в зависимости от капсида, которые лишены всех вирусных генов и поэтому демонстрируют улучшенный профиль б

Совпадение в аннотации оригинала
Genome editing of hematopoietic stem cells (HSCs) represents a therapeutic option for a number of hematological genetic diseases, as HSCs ha … anemia, hemophilia, and HIV-1 infection by ex vivo and in vivo editing in transgenic mice, nonhuman primates, as well as in human CD34+ cells. Mechanisms of therapeutic gene transfer including episomal expression of designer nucleases and base editors, transposase-mediated random integration, and targeted homology-directed repair triggered integration into …

Thoracic radiography of healthy captive male and female Squirrel monkey (Saimiri spp.).

The purpose of this prospective study was to describe the normal anatomy and provide reference ranges for measurements of thoracic radiography on Squirrel monkeys (n = 13). Thoracic radiography is a common non-invasive diagnostic tool for both cardiac and non-cardiac thoracic structures. Furthermore cardiac disease is a common condition in captive primates. In this study, left-right lateral, right-left lateral and dorsoventral projections of 13 healthy Squirrel monkeys were reviewed during their annual health examinations. The mean Vertebral Heart Score on the left-right and right-left lateral…

An Alternative Treatment Against Acanthocephala ( Prosthenorchis elegans) in Captive Squirrel Monkeys ( Saimiri sciureus) in Mexico.

We provide the first report of Acanthocephala ( Prosthenorchis elegans) in Mexican non-human primates. There has been no known treatment against this parasite except for surgical removal, and this has been relatively ineffective because of the small juveniles. We report the presence of P. elegans in a captive breeding colony of squirrel monkeys ( Saimiri sciureus) in Mexico, and we describe a successful treatment protocol. Treatment involved 2 steps: oral administration of the drugs loperamide chlorhydrate (0.5 mg/0.9 kg/3 days) and niclosamide (0.2 mg/0.9 kg/3 days) followed by surgical remov…

Prophylactic orthosteric inhibition of leukocyte integrin CD11b/CD18 prevents long-term fibrotic kidney failure in cynomolgus monkeys.

Ischaemic acute kidney injury (AKI), an inflammatory disease process, often progresses to chronic kidney disease (CKD), with no available effective prophylaxis. This is in part due to lack of clinically relevant CKD models in non-human primates. Here we demonstrate that inhibition of the archetypal innate immune receptor CD11b/CD18 prevents progression of AKI to CKD in cynomolgus monkeys. Severe ischaemia-reperfusion injury of the right kidney, with subsequent periods of the left ureter ligation, causes irreversible right kidney failure 3, 6 or 9 months after AKI. Moreover, prophylactic inacti…

Immunopathology of Chikungunya Virus Infection: Lessons Learned from Patients and Animal Models.

Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes acute and chronic arthritis. The virus reemerged in the Indian Ocean … tions of CHIKV that define the disease and the use of relevant animal models, from mice to nonhuman primates, are discussed. Understanding key cellular factors in CHIKV infection and the interplay with the immune system will aid in the development of preventive and therapeutic approaches to combat this painful viral disease in humans.

ALD1613, a Novel Long-Acting Monoclonal Antibody to Control ACTH-Driven Pharmacology.

Adrenocorticotropic hormone (ACTH) is the primary regulator of adrenal glucocorticoid production. Elevated levels of ACTH play a critical ro … corticosterone levels were significantly reduced by ALD1613. Administration of ALD1613 to nonhuman primates on days 1 and 7 stably reduced plasma cortisol levels >50% for 57 days. ALD1613 demonstrates the potential of a monoclonal antibody to be an effective therapeutic for conditions with elevated ACTH levels.

Cardiorespiratory effects of epidural anesthesia using lidocaine with morphine or dexmedetomidine in capuchin monkeys (Sapajus sp.) undergoing bilateral tubal ligation surgery, anesthetized with isoflurane.

BACKGROUND: Epidural anesthesia is indicated to decrease other anesthetic requirements, prolong analgesia, and reduce side effects. In primates, its use has been scarcely described. The aim was to evaluate the cardiorespiratory effects of epidural anesthesia with lidocaine and dexmedetomidine (DEX) or morphine (MOR). METHODS: Ten female capuchin monkeys (Sapajus sp.) received epidural anesthesia with lidocaine and DEX or MOR under general anesthesia. RESULTS: There was a significant decrease in heart rate with DEX and in blood pressure in all groups, with no changes in SpO2 . There was a sig…

Ebola virus infection kinetics in chimeric mice reveal a key role of T cells as barriers for virus dissemination.

Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b+ DCs in n…

Dental disorders in brown howler monkeys (Alouatta guariba clamitans) maintained in captivity.

BACKGROUND: The aim of this study was to investigate dental disorders of brown howler monkeys maintained in captivity. The hypothesis is that the identification and diagnosis of the lesions may contribute to control and prevention. METHODS: Sixteen intact brown howler monkeys (Alouatta guariba clamitans), eight females and eight males, weighing from 3.9 to 6.8 kg, were studied. Under general anesthesia, the teeth were evaluated by visual inspection, probing, palpation, and intra-oral radiographic exam. The findings were registered on a dental chart specific for primates. RESULT: Of the 16 mo…

Yellow fever outbreaks in São Paulo State, Brazil, 2000-2010.

OBJECTIVE: to describe yellow fever occurrence in the state of São Paulo, Brazil, in the period 2000-2010. METHODS: this was a descriptive study using data regarding human cases, epizootics in non-human primates and virus vector isolation in São Paulo State, between 2000 and 2010. RESULTS: three sylvatic yellow fever outbreaks were registered in the state with 32 human cases and 15 deaths; the cases occurred in unvaccinated individuals exposed to the sylvatic form of transmission; epizootics was confirmed before the virus began circulating in humans in the region of São José do Rio Preto and…

Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site.

Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and ∼200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The struct…

Конвергентный захват ретровирусных суперантигенов млекопитающими герпесвирусами.

Горизонтальная передача генов от ретровирусов млекопитающим хорошо задокументирована и обширна, но редко между не связанными вирусами с различными типами генома. Три герпесвируса кодируют ген с сходством с ретровирусным суперантигенным геном (саг) не связанного с вирусом опухоли мыши (MMTV). Мы открываем древние ретровирусные связки у более чем 20 млекопитающих, чтобы восстановить их общую историю с герпесвирами, показав, что приобретение является конвергентным эволюционным событием. Ретровирус, распространявшийся в южноамериканских приматах более 10 миллионов лет назад, был источником герпесв

Совпадение в аннотации оригинала
Horizontal gene transfer from retroviruses to mammals is well documented and extensive, but is rare between unrelated viruses with distinct … that the acquisition is a convergent evolutionary event. A retrovirus circulating in South American primates over 10 million years ago was the source of sag in two monkey herpesviruses, and a different retrovirus was the source of sag in a Peruvian rodent herpesvirus. We further show through a timescaled phylogenetic analysis that a cross-species transmiss …