Virus-specific T cell responses in macaques acutely infected with SHIV(sf162p3)

CD4(+) T helper and CD8(+) cytotoxic T lymphocyte responses are believed to play an important role in the control of primary HIV and SIV infection. However, the role of these cells in macaques acutely infected with SHIV(sf162p3) has not been well characterized. In this study, ten adult rhesus macaques were intravaginally infected with SHIV(sf162p3), and antigen-specific cytokine responses to SHIV-Tat, Nef, Gag and Env peptide pools were examined through 70 days post inoculation (p.i.) using ELISPOT and/or cytokine flow cytometry (CFC). Peak plasma viral replication occurred between 14 and 21 days p.i. followed by low to undetectable plasma viremia by 70 days of infection in most macaques. Although some animals had strong virus-specific cellular immune responses, many had weak or minimal responses that did not correlate with the post peak decline in plasma viremia.     

DNA/MVA HIV-1/AIDS vaccine elicits long-lived vaccinia virus-specific immunity and confers protection against a lethal monkeypox challenge

Modified vaccinia Ankara (MVA) is being tested in humans as an alternative to the current smallpox vaccine Dryvax. Here, we compare the magnitude and longevity of protective immune responses elicited by a DNA/MVA HIV-1 vaccine with those elicited by Dryvax using a monkeypox virus/macaque model. The DNA/MVA vaccine elicited similar levels of vaccinia virus (VV)-specific antibody and 5-10-fold lower levels of VV-specific cellular responses than Dryvax. This MVA-elicited cellular and humoral immunity was long-lived. A subset of the DNA/MVA- and Dryvax-vaccinated macaques were subjected to a lethal monkeypox virus challenge at 3 years after vaccination. All of the vaccinated monkeys survived, whereas the unvaccinated controls succumbed to monkeypox. The viral control correlated with early postchallenge levels of monkeypox-specific neutralizing antibody but not with VV-specific cellular immune response. Thus, our results demonstrate the elicitation of long lasting protective immunity for a lethal monkeypox challenge by a DNA/MVA HIV-1 vaccine.     

Distribution of ABO/Rh blood groups and their association with hepatitis B virus infection in 3.8 million Chinese adults: A population‐based cross‐sectional study

ABO and Rh blood groups play a vital role in blood transfusion safety and clinical practice and are thought to be linked with disease susceptibility. The results from previous studies that focused on the association between blood groups and HBV infection remain controversial. China has the world's largest burden of HBV infection. We assessed the distribution of ABO/Rh blood groups in Chinese adults and examined the association between these groups and HBV infection. We did a nationwide cross‐sectional study using data from a physical check‐up programme from 31 provinces examined between 2010 and 2012. ELISA was used to test for HBsAg in serologic samples. Multivariable logistic regression was used to estimate aOR of the association between ABO and Rh blood groups and HBV infection. Among 3 827 125 participants, the proportion of participants with blood group A was highest (30.54%), followed by O (30.37%), B (29.42%) and AB (9.66%). A total of 38 907 (1.02%) were Rh‐D negative. The prevalence of HBsAg in blood groups O, A, B and AB were 6.34%, 5.55%, 5.18% and 5.06%, respectively. HBsAg prevalence was 5.65% in Rh‐D‐positive and 3.96% in Rh‐D‐negative participants. After controlling for other potential risk factors, multivariate models showed that participants with blood group O (adjusted OR = 1.22, 95% CI: 1.20‐1.25) were at higher risk of HBV infection compared with group AB. Rh‐D‐positive participants (adjusted OR = 1.44, 95% CI: 1.37‐1.52) were at higher risk of HBV infection than Rh‐D‐negative participants. The associations between ABO/Rh blood groups and HBV infection were similar in subgroup analysis. The proportions of O, A, B and AB blood groups were approximately 3:3:3:1, and nearly 1 in 100 people was Rh‐D negative among Chinese adults. Blood group O and Rh‐D positivity were both associated with increased HBV infection. The risk of HBV infection and blood safety should be taken into consideration in clinical practice, especially when transfusing those with blood group O. Awareness and prevention of HBV infection is of particular importance for individuals with blood group O.     

Unique pattern of enzootic primate viruses in Gibraltar macaques

Because Gibraltar's macaques (Macaca sylvanus) have frequent contact with humans, we assayed 79 macaques for antibodies to enzootic primate viruses. All macaques were seronegative for herpesvirus B, simian T-cell lymphotropic virus, simian retrovirus, simian immunodeficiency virus, and rhesus cytomegalovirus. Seroprevalence of simian foamy virus reached 88% among adult animals.     

Distribution of protein phosphatases-1 alpha and -1 gamma 1 and the D(1) dopamine receptor in primate prefrontal cortex: Evidence for discrete populations of spines.

The function of G protein-coupled receptors depends on the availability of the appropriate signal transduction proteins in close proximity to the receptor. We have examined and quantified in primate prefrontal cortex the subcellular distribution of two isoforms of protein phosphatase-1 (PP1), PP1 alpha and PP1 gamma 1, which are components of the signal transduction pathway accessed by the D(1) dopamine receptor. Both PP1 alpha- and PP1 gamma 1-labeled puncta are seen in cortex, basal ganglia, hippocampus, and thalamus. Viewed with the electron microscope, both PP1 isoforms are selectively localized to dendritic spines and are found in different percentages of spines; PP1 alpha is present in roughly 70% and PP1 gamma 1 in roughly 40% of dendritic spines. Our analysis indicates that three populations of spines are defined by the distribution of these PP1 isoforms: those that contain both PP1 alpha and PP1 gamma 1, those that contain only PP1 alpha and those that contain neither. The D(1) receptor is present in a subset of the population that contains both PP1 alpha and PP1 gamma 1. The nonhomogeneous distribution of signal transduction proteins in the spines and dendrites of cortical pyramidal cells may help to explain differences in the actions of receptors that nominally use the same signal-transduction pathway.     

Cortical projections of the non-entorhinal hippocampal formation in the cynomolgus monkey (Macaca fascicularis)

Episodic memory consolidation requires the integrity of the anatomical pathways between the cerebral cortex and the hippocampal formation. Whilst the largest cortical output of the hippocampal formation originates in the entorhinal cortex, direct projections from CA1, subiculum and presubiculum to the cortex have been reported. The aim of this study is the assessment of the extent, topography and relative strength of those projections, as a parallel/alternate route of memory processing. A total of 45 injections in 28 Macaca fascicularis monkeys were used. Cortical deposits of fluorescent tracers (20 cases, 3% Fast Blue, 2% Diamidino Yellow) or 1% WGA-HRP (eight cases) were made in different cortical areas of the frontal, temporal and parietal lobes, as well as cingulate cortex by direct exposure of the cortical surface. After appropriate survival, animals were perfused and the brains serially sectioned at 50 microm and the retrograde labelling charted with an X-Y digitizing system. Retrograde neuronal labelling was observed in CA1, subiculum, presubiculum and parasubiculum; it was absent in the dentate gyrus, CA3 and CA2. Compared to other portions of the hippocampal formation, the CA1-subiculum border had the highest number of labelled neurons (especially after deposits in the rostral perirhinal cortex), followed by medial frontal cortex, temporal pole, orbitofrontal, anterior and posterior cingulate cortices, parietal and inferotemporal cortices, and no labelling after posterior inferotemporal and lateral frontal cortices. Our results indicate that CA1, subiculum, presubiculum and parasubiculum send direct output to cortical areas. This nonentorhinal, hippocampal formation cortical output may be relevant in memory processing.     

血管生成素1对高糖环境中猴脉络膜-视网膜内皮细胞的保护作用

目的 探讨高浓度葡萄糖对内皮细胞（endothelial cell,EC）单层通透性模型通透性的影响以及血管生成素1（angiopoietin-1,Ang-1）对此的保护作用。方法 将猴脉络膜-视网膜内皮细胞（RF/6A）接种于孔径0.8 μm聚碳酸酯微孔滤膜中,形成致密单层后分三组培养。正常对照组：DMEM高糖培养基,含葡萄糖25 mmol/L;高糖组：DMEM培养基,含葡萄糖40 mmol/L;Ang-高糖组：DMEM培养基,含葡萄糖40 mmol/L＋Ang-1 250 ng/ml。于第1天、第3天、第5天、第7天4个时间点建立EC单层通透性模型,检测蛋白质渗透压反射系数（δ）及滤过系数（Kf）,以监测EC单层通透性的变化;利用Western blot（NBT/BCIP显色法）检测第5天时survivin的表达。结果 第3天、第5天及第7天时,高糖组EC单层通透性增高（P〈0.01）,Ang-高糖组在第5天及第7天时,EC单层通透性升高（P〈0.01）,但仍低于高糖组;Western blot结果显示,Ang-高糖组survivin表达明显高于其他各组（P〈0.01）。结论 高糖能够增加EC单层通透性,Ang-1能对抗高糖的这种生物学作用。它可能是通过上调凋亡抑制基因survivin的表达,抑制RF/6A的凋亡而发挥生物学作用。     

Role of histo-blood group antigens in primate enteric calicivirus infections

Human noroviruses (NoV) are associated with large proportion of non-bacterial diarrhea outbreaks together with > 50% of food-associated diarrheas. The function of histo-blood group antigens (HBGAs) in pathogenesis of virus infection was implicated. Until recently however, due to lack of a robust animal and in vitro models of human NoV infection, only the partial knowledge concerning the virus pathogenesis (receptor, co-receptor and target cell) and absence of viable vaccine candidates were the frequently referenced attributes of this acute diarrheal illness. Recently, a novel group of enteric caliciviruses (CV) of rhesus macaque host origin was discovered and described. The new genus within the family Caliciviridae was identified: Rhesus Enteric CV, i.e., “Recovirus” (ReCV). ReCVs are genetically and biologically close relatives of human NoVs, exhibit similar genetic and biological features and are capable of being propagated in cell culture. ReCVs cause symptomatic disease (diarrhea and fever) in experimentally inoculated macaques. Formulation and evaluation of efficient NoV vaccine might take several years. As suggested by recent studies, inhibition of HBGAs or HBGA-based antivirals could meanwhile be exploited as vaccine alternatives. The purpose of this minireview is to provide the guidance in respect to newly available primate model of enteric CV infection and its similarities with human NoV in utilizing the HBGAs as potential virus co-receptors to indirectly address the unresolved questions of NoV pathogenesis and immunity.     

Prolonged High-Level Detection of Retrovirally Marked Hematopoietic Cells in Nonhuman Primates after Transduction of CD34+ Progenitors Using Clinically Feasible Methods

Low-level retroviral transduction and engraftment of hematopoietic long-term repopulating cells in large animals and humans remain primary obstacles to the successful application of hematopoietic stem cell (HSC) gene transfer in humans. Recent studies have reported improved efficiency by including stromal cells (STR), or the fibronectin fragment CH-296 (FN), and various cytokines such as flt3 ligand (FLT) during ex vivo culture and transduction in nonhuman primates. In this work, we extend our studies using the rhesus competitive repopulation model to further explore optimal and clinically feasible peripheral blood (PB) progenitor cell transduction methods. First, we compared transduction in the presence of either preformed autologous STR or immobilized FN. Long-term clinically relevant gene marking levels in multiple hematopoietic lineages from both conditions were demonstrated in vivo by semiquantitative PCR, colony PCR, and genomic Southern blotting, suggesting that FN could replace STR in ex vivo transduction protocols. Second, we compared transduction on FN in the presence of IL-3, IL-6, stem cell factor (SCF), and FLT (our best cytokine combination in prior studies) with a combination of megakaryocyte growth and development factor (MGDF), SCF, and FLT. Gene marking levels were equivalent in these animals, with no significant effect on retroviral gene transfer efficiency assessed in vivo by the replacement of IL-3 and IL-6 with MGDF. Our results indicate that SCF/G-CSF-mobilized PB CD34⁺ cells are transduced with equivalent efficiency in the presence of either STR or FN, with stable long-term marking of multiple lineages at levels of 10–15% and transient marking as high as 54%. These results represent an advance in the field of HSC gene transfer using methods easily applied in the clinical setting.     

The development of auditory event related potentials in the rhesus monkey (Macaca mulatta)

Auditory event related potentials were recorded from neonatal, 3‐month, and 3‐year old rhesus monkeys. Auditory brainstem evoked responses (ABRs) were reliably recorded at all ages. ABR latencies decreased with age. Age effects were greater the more centrally generated the wave. Wave I amplitude decreased with age, Wave II increased, and Wave IV remained about the same. Stimulus rate effects were greater in neonates than older monkeys. Stimulus frequency also affected the ABR, but not differentially as a function of age. Recording montage had a significant effect on the recorded waveform. Wave I tended to be larger in amplitude in horizontal recordings and front–back recordings, while the later waves were relatively more prominent in more vertical montages. Middle latency evoked responses and late potentials were less reliably recorded than the ABR. Their reproducibility improved with age. Auditory event related potentials are promising measures of auditory function for research requiring nonhuman primate models of the developing human. © 1999 John Wiley & Sons, Inc. Dev Psychobiol 34: 37–56, 1999