Infected Monkeys Research Articles

Epidemic of venereal treponematosis in wild monkeys: a paradigm for syphilis origin.

Treponema pallidum infections have been primarily known as slightly contagious mucocutaneous infections called yaws (tropical Africa and America) and bejel (subtropical North Africa). T. pallidum emerged as a highly infectious venereal syphilis agent in South America, probably about 500 years ago, and because of its venereal transmission, it quickly caused a worldwide pandemic. The disease manifests as lesions, including a chancre; then antibodies become detectable when or slightly after the chancre appears, and before the development of a rash and other systemic manifestations. Venereal diseases are poorly known in monkeys. During fieldwork in Senegal, we discovered an epizootic outbreak of venereal disease that we explored. We detected a venereal form of T. pallidum subsp. pertenue infection in green monkeys (Chlorocebus sabaeus), then observed an epizootic outbreak in Senegal and its spread among baboons a year later. Comparative analysis of T. pallidum genomes from the monkeys' chancres and other Treponema genomes showed an acceleration of the number of single nucleotide polymorphisms, comparable to that observed in syphilis. Identified T. pallidum clones seem to be epizootic through the acceleration of their mutation rate, which is linked to their larger diffusion.

Keragaman dan Prevalensi Nematoda Parasit Usus pada Monyet Ekor Panjang (Macaca fascicularis) di Kawasan Wisata “Masjid Saka Tunggal”

Nematode parasites generally found around the world. Research on intestinal parasitic nematodes in long-tailed monkeys ( Macaca fascicularis ) has been carried out in Cikakak Village, Banyumas Regency. The aims of the research was to find out the diversity and prevalence of Nematodes parasite on long tail monkey. Survey methods was used in this research with determine the eggs of the nematodes parasite on faeces of 30 adults and 30 adolescence of monkey. The results of the study found five types of intestinal parasitic nematodes classified as Soil Transmitted Helminths namely Strongyloides sp. Ascaris sp. Trichuris sp. Ancylostoma sp. Oeshopagustomum sp. The parasitic diversity index value (H ') indicates moderate (moderate) community stability. Parasitic nematodes in adolescent long-tailed monkeys are relatively similar to adult monkeys. The prevalence of long-tailed monkeys infected with parasitic nematodes is quite high at 40.5 ± 13.5. The prevalence of long-tailed monkeys in adolescence is higher than the prevalence of adult long-tailed monkeys, nematode infections in long-tailed monkeys in Cikakak Village are more single infections. It can be concluded that long tail monkey at Cikakak have been infected by Nematodes parasites and this result can be used to population management of long tail monkey at this area.

Georg Schaltenbrand (1897-1979) and his research without moral boundaries on multiple sclerosis

In 1953 the prominent German neurologist Georg(es) Schaltenbrand became president of the German Neurological Society (DGN) and in 1967 honorary president. Less well known is the fact that from 1933 to 1936 he was member of the "Stahlhelm" and the Storm Troopers (SA). In 1937 he joined the National Socialist German Workers' Party (NSDAP) and other Nazi organizations. For the last three decades Schaltenbrand's name has primarily been associated with human experiments performed in 1940. His objective was to prove the viral etiology of multiple sclerosis (MS). To that end he injected cerebrospinal fluid (CSF) drawn from allegedly infected monkeys and MS patients into severely handicapped patients from the psychiatric asylum Werneck near Schweinfurt as well as into severely ill patients from the University Hospital of Würzburg without their consent. Weeks later he withdrew CSF samples from the recipients, sometimes repeatedly to control parameters of inflammation. Although not all details of his test series can be clarified, there is no doubt that he violated prevailing laws and ethical standards. According to the present state of knowledge, he was the only German professor of neurology during the Nazi era who performed such experiments on humans in terms of "research without moral boundaries". He later justified his actions by arguing that he had intended to exert apositive effect on the mentally ill. Judicial investigations ended in 1948 without an indictment. Long after his death, in 1994 the "Schaltenbrand experiments" became known to awider public and three years later the Medical Faculty of Würzburg condemned the unethical research and distanced itself from its former member. Today, Schaltenbrand's study is assessed as an unacceptable form of research on particularly vulnerable patients for the benefit of third parties. As aresult, ethical norms formulated in the 1930s were reinforced by international guidelines, e.g. the Declaration of Helsinki drafted by the World Medical Association.

Woolly Monkey-HBV Infection in Squirrel Monkeys as a Surrogate Nonhuman Primate Model of HBV Infection.

Development of curative therapies for chronic hepatitis B virus (HBV) infection will likely require new animal models. Here, we evaluate HBV infection in squirrel monkeys based on the high‐sequence homology of the HBV receptor, Na+/taurocholate co‐transporting peptide (NTCP), between humans and squirrel monkeys. HBV PreS1 peptide was examined for binding human and squirrel monkey NTCP. Immunodeficient Fah −/−, NOD, Rag1 −/−, Il2Rg null (FNRG) mice engrafted with human or squirrel monkey hepatocytes were challenged with HBV or Woolly Monkey HBV (WMHBV). In addition, adult squirrel monkeys were inoculated with HBV, WMHBV, adeno‐associated virus containing an infectious genome of HBV (AAV‐HBV), and AAV‐WMHBV. Finally, neonate squirrel monkeys were assessed for the potential of chronic infection with WMHBV. PreS1 peptide efficiently bound to human and squirrel monkey NTCP but not to mouse or capuchin NTCP. FNRG mice engrafted with squirrel monkey hepatocytes were susceptible to infection by WMHBV but not human HBV. Similarly, adult squirrel monkeys could be infected with WMHBV but not human HBV, whereas chimeric mice engrafted with human hepatocytes were susceptible to HBV but not WMHBV. Infection of squirrel monkeys with AAV‐WMHBV yielded maximum viremia of 108 genomes/mL with detectable virus for up to 8 months. Notably, covalently closed circular DNA was detected in the liver of these animals. Infection of neonates with WMHBV led to detectable viremia for up to 6 months. Conclusions: Adult and neonate squirrel monkeys exhibited prolonged WMHBV viremia lasting 6‐8 months. This is greater than twice the duration of viremia achieved in other nonhuman primates and suggests that squirrel monkeys may be a suitable model for testing HBV therapeutics.

Transfusion transmitted HTLV-1 and incidence of HTLV-1 in South African blood donors

HTLV-1 occurs world-wide but is more prevalent in some areas including southern Japan, the Caribbean region, parts of South America, Sub-Saharan Africa and the Middle East, Australia and Melanesia (1-3). The reason for this unusual geographical distribution is not known. An interesting aspect of this virus is that only a few nucleotide substitutions are observed among virus strains of HTLV-1. This variability of nucleotides is specific to the geographical origin of the patients. HTLV-1 was originally acquired by humans through interspecies transmission from STLV-1 (simian T-cell leukaemia virus type 1) infected monkeys in Africa, Europe and Asia (1).

An Intranasal Exposure Model of Lethal Nipah Virus Infection in African Green Monkeys.

Due to the difficulty in conducting clinical trials for vaccines and treatments against Nipah virus (NiV), licensure will likely require animal models, most importantly non-human primates (NHPs). The NHP models of infection have primarily relied on intratracheal instillation or small particle aerosolization of NiV. However, neither of these routes adequately models natural mucosal exposure to NiV. To develop a more natural NHP model, we challenged African green monkeys with the Bangladesh strain of NiV by the intranasal route using the laryngeal mask airway (LMA) mucosal atomization device (MAD). LMA MAD exposure resulted in uniformly lethal disease that accurately reflected the human condition.

Markers of hepatitis A in the monkeys of the Adlers primate center.

The aim of this research was a comparative study of serological and molecular-genetic markers of HAV infection in monkeys born at the Adler Primate Center and in those imported from different countries. Fecal samples (n = 313) and serum (n = 266) from various species of monkey using ELISA and RT-PCR were studied. The frequency of anti-HAV-IgG was high (78.9%) in imported animals (vervet monkeys from Tanzania and cynomolgus monkeys from Vietnam) and as well as in various species of monkeys (rhesus monkeys, cynomolgus monkeys, green monkeys and papio hamadryas) of the Center (88.6%). At the same time, in the imported monkeys, the markers of "fresh" HAV infection (IgM-27.2%, Ag-HAV-16.7%, RNA-22.0%) were detected significantly more often (p> 0.05) than in monkeys kept at the Colony (IgM-7.5%, HAV-Ag - 5.2%, RNA - 3.6%). In general, anti-IgG reactivity ranged from 1.064 to 2.073 OD450, anti-IgM ranged from 0.546 to 1.059 OD450. The number of HAV-Ag was 0.496 - 1.995 OD450. RNA HAV only in rhesus monkeys and cynomolgys monkeys born at the Colony, as well as in imported vervet monkeys was detected. The data obtained indicate a wide circulation of HAV among monkeys born in the Adler Primate Center and among the imported animals. Markers of "fresh" HAV infection varied depending on the species of monkeys and their origin.

MOLECULAR TYPING OF METHICILLIN-SUSCEPTIBLE STAPHYLOCOCCUS AUREUS (MSSA), ISOLATED FROM MONKEYS, BASED ON COAGULASE GENE POLYMORPHISM

Staphylococcus aureus is a very dangerous microorganism that causes more than 100 nosological forms of disease in humans and animals, including pneumonia, skin and soft tissue infections, food toxicoinfections, wound abscess, etc. Numerous studies on genotyping Staphylococcus aureus, isolated from humans, food and bovine mastitis have been carried out. The lack of information on the genotyping of these pathogens detected in monkeys living in captivity served as a stimulus to conduct a similar research, since staphylococcal infections in the primates are widespread. The present study is devoted to the study of the polymorphism of a variable region of the coagulase gene and to the typing of Staphylococcus aureus isolates from monkeys of different species kept at Adler monkey farm. 115 Staphylococcus aureus isolates were studied using phenotypic and molecular genetic methods. Genotyping was performed using PCR, real-time PCR and PCR with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). A real-time PCR analysis allowed to classify all Staphylococcus aureus as methicillin-susceptible staphylococci (MSSA). After amplification of a variable region of the coagulase gene, 4 types of amplicons of 600, 700, 800, and 900 bp were generated. This data demonstrates structural differences of this gene in the studied isolates. The coagulase gene of 900 bp prevailed. The use of the Cfo1 endonuclease allowed to identify 23 different restriction profiles of the coa gene, but only three of them predominated. Staphylococcus aureus bacteria with seven types of coagulase gene were found only in the lungs of monkeys that died of pneumonia. The results obtained suggest that these isolates have tropism for lung tissue. Among Staphylococcus aureus isolated from pneumonia cases, isolates with three types of the coa gene prevailed. Staphylococcus aureus of eleven types of coagulase gene can be attributed to the invasive isolates, since they were detected in the tissues of various organs. Staphylococcal infection in monkeys kept at the monkey farm is caused by genotypically heterogeneous population of Staphylococcus aureus.

Global phosphoproteomic analysis of Ebola virions reveals a novel role for VP35 phosphorylation-dependent regulation of genome transcription.

Ebola virus (EBOV) causes severe human disease with a high case fatality rate. The balance of evidence implies that the virus circulates in bats. The molecular basis for host-viral interactions, including the role for phosphorylation during infections, is largely undescribed. To address this, and to better understand the biology of EBOV, the phosphorylation of EBOV proteins was analyzed in virions purified from infected monkey Vero-E6 cells and bat EpoNi/22.1 cells using high-resolution mass spectrometry. All EBOV structural proteins were detected with high coverage, along with phosphopeptides. Phosphorylation sites were identified in all viral structural proteins. Comparison of EBOV protein phosphorylation in monkey and bat cells showed only partial overlap of phosphorylation sites, with shared sites found in NP, VP35, and VP24 proteins, and no common sites in the other proteins. Three-dimensional structural models were built for NP, VP35, VP40, GP, VP30 and VP24 proteins using available crystal structures or by de novo structure prediction to elucidate the potential role of the phosphorylation sites. Phosphorylation of one of the identified sites in VP35, Thr-210, was demonstrated to govern the transcriptional activity of the EBOV polymerase complex. Thr-210 phosphorylation was also shown to be important for VP35 interaction with NP. This is the first study to compare phosphorylation of all EBOV virion proteins produced in primate versus bat cells, and to demonstrate the role of VP35 phosphorylation in the viral life cycle. The results uncover a novel mechanism of EBOV transcription and identify novel targets for antiviral drug development.

Nonclinical safety of tildrakizumab, a humanized anti–IL-23p19 monoclonal antibody, in nonhuman primates

Tildrakizumab (also known as MK-3222), is a high-affinity, humanized, immunoglobin G1κ monoclonal antibody targeting the p19 subunit of interleukin-23 recently approved for the treatment of moderate to severe plaque psoriasis in the US, Europe, and Australia. The safety profile of tildrakizumab was characterized in nonclinical studies using a pharmacologically relevant cynomolgus monkey model. In repeat-dose toxicity studies, cynomolgus monkeys were chronically treated with subcutaneous (SC) injections of 100 mg/kg of tildrakizumab every 2 weeks up to 9 months. Tildrakizumab was well tolerated, with no toxicological findings (including assessment of reproductive organs; hormonal effects; and cardiovascular, respiratory, and central nervous system function) at systemic exposures approximately 90 times higher than the recommended human dose of 100 mg. An embryofetal developmental study conducted in pregnant monkeys revealed no treatment-related effects to the developing fetus following SC administration of tildrakizumab 100 mg/kg. In a pre- and postnatal development study, 2 neonatal deaths due to potential viral infection at 100 mg/kg were considered of uncertain relationship to the treatment based on a lack of historical data on the occurrence of viral infection in neonate cynomolgus monkeys. The results of this comprehensive nonclinical safety program support the safe use of tildrakizumab.

In vitro responses of multiple cytokines to purified protein derivative in healthy and naturally Mycobacterium tuberculosis-infected rhesus monkeys (Macaca mulatta).

As the widely used biomarker of whole-blood stimulation assays for tuberculosis diagnosis, the release of IFN-γ might be affected by multiple factors, such as immunosuppression and some infectious agents. Here, we evaluated additional cytokines as diagnostic biomarkers. Forty-three cytokines were measured by Luminex xMAP technologies in 30 healthy and 10 naturally Mycobacterium tuberculosis (MTB)-infected rhesus monkeys pre- and post-stimulation by purified protein derivative (PPD). After stimulation, production of 23 and 38 cytokines was markedly increased in healthy and MTB-infected macaques, respectively. A comparison of the stimulation index (SI) between MTB infections and healthy macaques showed that the SIs of 32 cytokines in MTB-infected macaques were significantly higher than those in healthy macaques. Pooling the results, eight cytokines were suggested as ideal biomarkers for a whole-blood stimulation assay for MTB diagnosis. PPD could induce multiple cytokine responses in either healthy or MTB-infected monkeys, and eight cytokines had reliable predictive capacity as diagnostic biomarkers of MTB infection.

Efficacy of clarithromycin against H5N1 and H7N9 avian influenza a virus infection in cynomolgus monkeys

Clarithromycin (CAM), a 14-membered ring macrolide, has anti-inflammatory and immunomodulatory actions and antiviral effects in seasonal influenza virus infection. We examined the prophylactic and therapeutic efficacy of CAM against H5N1 highly pathogenic and H7N9 low pathogenic avian influenza virus infections in cynomolgus monkeys. CAM suppressed H5N1 virus-induced severe signs of disease in the treated monkeys and inhibited virus propagation in tracheal samples and the production of inflammatory cytokines in the lungs of monkeys infected with H5N1 and H7N9 viruses. The prophylactic administration of CAM showed more suppressive effects on clinical signs of disease and viral titers than did therapeutic administration. Thus, since administration of CAM alone showed a tendency to ameliorate clinical sings and to reduce levels of inflammatory cytokines, the macrolides are expected to have effects in combination with the other antiviral drugs on the prophylactic and treatment of patients with severe avian influenza virus infection, which should be further investigated.

Recent Incidence of Human Malaria Caused by Plasmodium knowlesi in the Villages in Kudat Peninsula, Sabah, Malaysia: Mapping of The Infection Risk Using Remote Sensing Data

Plasmodium knowlesi (Pk) is a malaria parasite that naturally infects macaque monkeys in Southeast Asia. Pk malaria, the zoonosis transmitted from the infected monkeys to the humans by Anopheles mosquito vectors, is now a serious health problem in Malaysian Borneo. To create a strategic plan to control Pk malaria, it is important to estimate the occurrence of the disease correctly. The rise of Pk malaria has been explained as being due to ecological changes, especially deforestation. In this research, we analysed the time-series satellite images of MODIS (MODerate-resolution Imaging Spectroradiometer) of the Kudat Peninsula in Sabah and created the “Pk risk map” on which the Land-Use and Land-Cover (LULC) information was visualised. The case number of Pk malaria of a village appeared to have a correlation with the quantity of two specific LULC classes, the mosaic landscape of oil palm groves and the nearby land-use patches of dense forest, surrounding the village. Applying a Poisson multivariate regression with a generalised linear mixture model (GLMM), the occurrence of Pk malaria cases was estimated from the population and the quantified LULC distribution on the map. The obtained estimations explained the real case numbers well, when the contribution of another risk factor, possibly the occupation of the villagers, is considered. This implies that the occurrence of the Pk malaria cases of a village can be predictable from the population of the village and the LULC distribution shown around it on the map. The Pk risk map will help to assess the Pk malaria risk distributions quantitatively and to discover the hidden key factors behind the spread of this zoonosis.

Association Between Simian Virus 40 and Human Tumors.

Simian virus 40 (SV40) is a small DNA tumor virus of monkey origin. This polyomavirus was administered to human populations mainly through contaminated polio vaccines, which were produced in naturally infected SV40 monkey cells. Previous molecular biology and recent immunological assays have indicated that SV40 is spreading in human populations, independently from earlier SV40-contaminated vaccines. SV40 DNA sequences have been detected at a higher prevalence in specific human cancer specimens, such as the brain and bone tumors, malignant pleural mesotheliomas, and lymphoproliferative disorders, compared to the corresponding normal tissues/specimens. However, other investigations, which reported negative data, did not confirm an association between SV40 and human tumors. To circumvent the controversies, which have arisen because of these molecular biology studies, immunological researches with newly developed indirect ELISA tests were carried out in serum samples from patients affected by the same kind of tumors as mentioned above. These innovative indirect ELISAs employ synthetic peptides as mimotopes/specific SV40 antigens. SV40 mimotopes do not cross-react with the homologous human polyomaviruses, BKPyV, and JCPyV. Immunological data obtained from indirect ELISAs, using SV40 mimotopes, employed to analyze serum samples from oncological patients, have indicated that these sera had a higher prevalence of antibodies against SV40 compared to healthy subjects. The main data on (i) the biology and genetics of SV40; (ii) the epidemiology of SV40 in the general population, (iii) the mechanisms of SV40 transformation; (iv) the putative role of SV40 in the onset/progression of specific human tumors, and (v) its association with other human diseases are reported in this review.

Natural infection of captive cynomolgus monkeys (Macaca fascicularis) with hepatitis E virus genotype 4

Data on natural HEV infection of infection in monkeys are limited. We report a case of hepatitis E virus genotype 4 infection in captive non-human primates (cynomolgus monkeys) imported from Vietnam. Phylogenetic analysis demonstrated that HEV infection was not the result of spillover from single source of infection, but rather the persistent circulation of HEV-4 among cynomolgus monkeys or multiple infections by related strains from a human or swine reservoir.

Functional genomics of simian malaria parasites and host-parasite interactions.

Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained recognition among scientists and public health officials. Notwithstanding, these species and others including Plasmodium coatneyi have served for decades as sources of knowledge on the biology, genetics and evolution of Plasmodium, and the diverse ramifications and outcomes of malaria in their monkey hosts. Experimental analysis of these species can help to fill gaps in knowledge beyond what may be possible studying the human malaria parasites or rodent parasite species. The genome sequences for these simian malaria parasite species were reported during the last decade, and functional genomics research has since been pursued. Here research on the functional genomics analysis involving these species is summarized and their importance is stressed, particularly for understanding host–parasite interactions, and potentially testing novel interventions. Importantly, while Plasmodium falciparum and Plasmodium vivax can be studied in small New World monkeys, the simian malaria parasites can be studied more effectively in the larger Old World monkey macaque hosts, which are more closely related to humans. In addition to ex vivo analyses, experimental scenarios can include passage through Anopheline mosquito hosts and longitudinal infections in monkeys to study acute and chronic infections, as well as relapses, all in the context of the in vivo host environment. Such experiments provide opportunities for understanding functional genomic elements that govern host–parasite interactions, immunity and pathogenesis in-depth, addressing hypotheses not possible from in vitro cultures or cross-sectional clinical studies with humans.

Evidences of HEV genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (Macaca fascicularis).

Hepatitis E virus genotype 3 (HEV-3) is an emerging zoonotic pathogen, responsible for sporadic cases of acute hepatitis E worldwide. Primate models have proven to be an essential tool for the study of HEV pathogenesis. Here we describe the outcomes of HEV infection in Macaca fascicularis (cynomolgus) inoculated experimentally with genotype 3. Eight adult cynomolgus macaques were inoculated intravenously with HEV-3 viral particles isolated from swine and human samples. Liver, spleen, duodenum, gallbladder and bile were sequential assessed up to the end-point of this study, 67 days post-inoculation (dpi). Our previously published findings showed that biochemical parameters return gradually to baseline levels at 55 dpi, whereas anti-HEV IgM and HEV RNA become undetectable in the serum and feces of all animals, indicating a non-viremic phase of recovery. Nevertheless, at a later stage during convalescence (67 dpi), the presence of HEV-3 RNA and antigen persist in central organs, even after peripheral viral clearance. Our results show that two cynomolgus inoculated with swine HEV-3 (animals I3 and O1) presented persistence of HEV RNA low titers in liver, gallbladder and bile. At this same stage of infection, HEV antigen (HEV Ag) could be detected in all infected animals, predominantly in non-reactive Kupffer cells (CD68+iNOS-) and sinusoidal lining cells. Simultaneously, CD4+, CD3+CD4+, and CD3+CD8+ immune cells were identified in hepatic sinusoids and small inflammatory clusters of lobular mononuclear cells, at the end-point of this study. Inability of HEV clearance in humans can result in chronic hepatitis, liver cirrhosis, with subsequent liver failure requiring transplantation. The results of our study support the persistence of HEV-3 during convalescence at 67 dpi, with active immune response in NHP. We alert to the inherent risk of viral transmission through liver transplantation, even in the absence of clinical and biochemical signs of acute infection. Thus, besides checking conventional serological markers of HEV infection, we strongly recommend HEV-3 RNA and antigen detection in liver explants as public health measure to prevent donor-recipient transmission and spread of hepatitis E.

Comparison of HEp-2 and Vero Cell Responses Reveal Unique Proapoptotic Activities of the Herpes Simplex Virus Type 1 α0 Gene Transcript and Product.

Previous studies have provided evidence suggesting a role for apoptosis in the control of Herpes Simplex Virus 1 (HSV-1) latency. HSV-1 induces and then later blocks apoptosis in infected cells. The immediate early viral gene α0, which synthesizes the ICP0 protein, is necessary and sufficient for HSV-1-induced apoptosis in human epithelial (HEp-2) cells. While previous research showed that ICP0 protein synthesis is not necessary for HSV-1-induced apoptosis in infected HEp-2 cells, circumstantial evidence suggested that it might be needed in infected African green monkey kidney (Vero) cells. In this study, we determined the specific aspects of α0 needed to trigger apoptosis in these two cell types. HEp-2 cells transfected with α0 expressing plasmids that generated either full-length, truncated, or no detectable (multiple stop codons) ICP0 protein died through apoptosis. This indicates that ICP0 protein is not necessary for α0-induced apoptosis and that α0 mRNA alone has apoptotic induction properties in HEp-2 cells. We next investigated the primary structure of α0’s mRNA to better define its proapoptotic ability. Since α0 is one of the few HSV-1 genes that are spliced, we transfected cells with a plasmid expressing ICP0 from cDNA copy, pcDNAICP0. The cells transfected with pcDNAICP0 underwent apoptosis at a level equivalent to those transfected with the genomic copy of α0, which indicates that neither splicing events nor introns are required for the apoptotic function of α0 in HEp-2 cells. Next, we studied the ability of α0 to cause apoptosis in Vero cells. Since HSV-1-induced apoptosis in Vero cells requires protein synthesis early in infection, proteins synthesized with immediate early kinetics may facilitate apoptosis. Vero cells were transfected with plasmids producing either full-length ICP0 or ICP0 truncated at codon 212. Full-length ICP0, but not truncated ICP0, induced apoptosis in Vero cells. Together, these results suggest that α0 gene expression triggers apoptosis, but ICP0 protein is needed to facilitate apoptosis in Vero cells. In addition, ICP0’s facilitation activity may lie in its carboxyl-terminated domain. Thus, our results demonstrate that α0’s mRNA and protein possess proapoptotic properties. The requirement for ICP0 protein during HSV-dependent apoptosis appears to be cell type specific.

Detection of Antibody and Antigen for Lassa Virus Nucleoprotein in Monkeys from Southern Nigeria

Lassa fever is a deadly viral haemorrhagic fever caused by Lassa Virus (LASV). Rodents, especially, Mystomys natalensis, are the known reservoirs of LASV and humans are the defined hosts. Monkeys share many illnesses with humans and experimental LASV infections in monkeys are fatal but natural LASV infection of monkeys has not been reported. Serum samples obtained between August 2015 and December 2017 from 62 monkeys belonging to six species in Southern Nigeria were tested for LASV as part of an ongoing surveillance of monkeys in the region for zoonotic pathogens. Commercially available Recombinant LASV (ReLASV) Pan-Lassa enzyme-linked immunosorbent assay (ELISA) test kits (Zalgen Labs, Germantown, MD, USA) were used to detect antibodies (IgG and IgM) and antigen specific for LASV nucleoprotein in the sera. Lassa-fever-specific IgG and IgM, and antigen specific for LASV nucleoprotein were detected in 5/62, 0/62, and 1/62 samples, respectively. The presence of LASV-specific antibodies in the sera suggests natural exposure to the virus, while the presence of LASV antigen may mean that monkeys are carriers of the virus. There is a need to broaden Lassa fever surveillance to include nonhuman primates (NHPs) for their probable role in the epidemiology of the disease.

Evaluation of epitope specificity in the immune response to PR8 H1N1 influenza virus infection in neonatal and adult African Green monkeys

Abstract Generation of effective antibody responses following virus infection is challenging in neonates as a result of impairments in the innate and adaptive immune systems that characterize early life. This leaves them particularly susceptible to severe disease following virus infection, e.g. influenza A virus. A potential contributor to the efficacy of the immune response generated following infection is the epitope specificity of the elicited antibodies. Previous studies in adult mice have reported a defined and reproducible pattern of immunodominance among antibodies directed to the neutralizing epitopes on the head of the influenza hemagglutinin (HA) molecule. The impact of age on the immunodominance pattern of HA-specific antibodies has not been explored. To address this, epitope recognition was quantified in plasma collected from newborn and adult African Green monkeys on d14 following PR8 influenza virus infection. For these analyses we used HA molecules engineered to singly express each of the neutralizing epitopes identified on the HA head. In addition, we used a construct that restricts recognition to the stem region of PR8 HA. Our analyses revealed a similar pattern of recognition by HA-specific IgG between infants and adults in the 14 day period following infection. In contrast, the HA-specific IgM pools exhibited distinct binding patterns in these two groups. The most striking of these differences was in the production of antibodies capable of recognizing the stem portion of HA. These data suggest antibody immunodominance patterns may be modulated with age and sheds new light on the regulation of potentially broadly protective stem responses to influenza virus.