Measles: What we have learned from non-human primate models

Studies in non-human primates (NHPs) have been crucial for our understanding of measles as a high impact viral disease of humans. Over a century ago, inoculations of NHPs with filtered secretions from measles patients first identified a virus as the causative agent of this disease. In the 1960s, studies in NHPs with measles virus isolates passaged in vitro provided the basis for live-attenuated measles virus vaccines, which became one of the most successful medical interventions in history. More recently, experimental infections of NHPs have provided critical contributions to our understanding of the tropism and pathogenesis of measles virus. This review briefly highlights some of the lessons learned from NHP models of measles virus infection

Impaired immunity in seals exposed to bioaccumulated environmental contaminants

Summary (En, Nl)Proefschrift (Doctor) - Erasmus Univ., Rotterdam (Netherlands). Title also in Dutc

Measles virus host invasion and pathogenesis

Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans and non-human primates. Measles is characterised by fever and skin rash and usually associated with cough, coryza and conjunctivitis. A hallmark of measles is the transient immune suppression, leading to increased susceptibility to opportunistic infections. At the same time, the disease is paradoxically associated with induction of a robust virus-specific immune response, resulting in lifelong immunity to measles. Identification of CD150 and nectin-4 as cellular receptors for measles virus has led to new perspectives on tropism and pathogenesis. In vivo studies in non-human primates have shown that the virus initially infects CD150+ lymphocytes and dendritic cells, both in circulation and in lymphoid tissues, followed by virus transmission to nectin-4 expressing epithelial cells. The abilities of the virus to cause systemic infection, to transmit to numerous new hosts via droplets or aerosols and to suppress the host immune response for several months or even years after infection make measles a remarkable disease. This review briefly highlights current topics in studies of measles virus host invasion and pathogenesis

Contaminant-induced immunotoxicity in harbour seals: Wildlife at risk?

Persistent, lipophilic polyhalogenated aromatic hydrocarbons (PHAHs) accumulate readily in the aquatic food chain and are found in high concentrations in seals and other marine mammals. Recent mass mortalities among several marine mammal populations have been attributed to infection by morbilliviruses, but a contributing role for immunotoxic PHAHs, including the polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) was not ruled out. We addressed this issue by carrying out a semi-field study in which captive harbour seals were fed herring from either the relatively uncontaminated Atlantic Ocean or the contaminated Baltic Sea for 2 years. We present here an overview of results obtained during this study. An impairment of natural killer (NK) cell activity, in vitro T-lymphocyte function, antigen-specific in vitro lymphocyte proliferative responses, and in vivo delayed-type hypersensitivity and antibody responses to ovalbumin was observed in the seals fed the contaminated Baltic herring. Additional feeding studies in PVG rats using the same herring batches suggested that an effect at the level of the thymus may be responsible for changes in cellular immunity, that virus-specific immune responses may be impaired, and that perinatal exposure to environmental contaminants represents a greater immunotoxic threat than exposure as a juvenile or adult. Together with the pattern of TCDD toxic equivalents of different PHAHs in the herring, these data indicate that present levels of PCBs in the aquatic food chain a

Complete genome sequence of phocine distemper virus isolated from a harbor seal (Phoca vitulina) during the 1988 North Sea epidemic

Phocine distemper virus (PDV) was identified as the cause of a large morbillivirus outbreak among harbor seals in the North Sea in 1988. PDV is a member of the family Paramyxoviridae, genus Morbillivirus. Until now, no full-genome sequence of PDV has been available

Haematology and clinical chemistry values for harbour seals (Phoca vitulina) fed environmentally contaminated herring remain within normal ranges

Abstract: Twenty-two young harbour seals (Phoca vitulina) were fed herring from either the relatively unpolluted Atlantic Ocean or the heavily polluted Baltic Sea as part of a 2½-year immunotoxicological study. Blood samples taken at regular intervals were analyzed for routine haematology and clinical chemistry. Minimal differences between the two groups were observed in these parameters over the course of the experiment. Of the 20 clinical chemistry parameters analyzed, slight differences were found in serum levels of urea, creatinine, magnesium, and cholesterol. In haematology profiles, red blood cell counts and haematocrit values were higher in seals fed Baltic herring, but these differences diminished over time. Neutrophil counts were also higher in this group of seals, especially during the second half of the feeding study. Factors affecting haematological and clinical chemistry parameters within feeding groups included gender, age, and season. The data collected demonstrate a relative insensitivity of clinical chemistry parameters to the effects of chronic exposure to environmental contaminants accumulated through the food chain, but suggest the induction of clear alterations in differential white blood cel

Morbillivirus infections of aquatic mammals: newly identified members of the genus.

Several disease outbreaks, which have caused the deaths of many thousands of seals and dolphins during the last decade, have now been attributed to infections with newly identified Morbilliviruses. Outbreaks in the late eighties amongst harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) in northwestern Europe and amongst baikal seals (Phoca sibirica) in Siberia were caused by the newly discovered phocine distemper virus and by a strain of canine distemper virus, respectively. Although closely related these two viruses were not identical. They were more distantly related to the viruses which caused mass mortality amongst striped dolphins (Stenella coeruleoalba) in the Mediterranean sea in the early nineties. This dolphin morbillivirus was shown to be closely related to a virus that was found in harbour porpoises (Phocoena phocoena) which had stranded at the coasts of northwestern Europe in the late eighties: porpoise morbillivirus. The present knowledge of the genetic and antigenic relationships of these apparently new members of the genus Morbillivirus with the established members of the genus is presented. In addition, the origin and epizootiological aspects of these newly discovered viruses are discussed. Finally experimental evidence that environmental pollution may have contributed to the severity and extent of these infections in recent years is presented

Morbillivirus infections: An introduction

Research on morbillivirus infections has led to exciting developments in recent years. Global measles vaccination coverage has increased, resulting in a significant reduction in measles mortality. In 2011 rinderpest virus was declared globally eradicated – only the second virus to be eradicated by targeted vaccination. Identification of new cellular receptors and implementation of recombinant viruses expressing fluorescent proteins in a range of model systems have provided fundamental new insights into the pathogenesis of morbilliviruses, and their interactions with the host immune system. Nevertheless, both new and well-studied morbilliviruses are associated with significant disease in wildlife and domestic animals. This illustrates the need for robust surveillance and a strategic focus on barriers that restrict cross-species transmission. Recent and ongoing measles outbreaks also demonstrate that maintenance of high vaccination coverage for these highly infectious agents is critical. This introduction briefly summarizes the most important current research topics in this field