Cytomegalovirus pp65 limits dissemination but is dispensable for persistence

The most abundantly produced virion protein in human cytomegalovirus (HCMV) is theimmunodominant phosphoprotein 65 (pp65), which is frequently included in CMVvaccines. Although it is nonessential for in vitro CMV growth, pp65 displaysimmunomodulatory functions that support a potential role in primary and/or persistentinfection. To determine the contribution of pp65 to CMV infection and immunity, wegenerated a rhesus CMV lacking both pp65 orthologs (RhCMVΔpp65ab). Whiledeletion of pp65ab slightly reduced growth in vitro and increased defective particleformation, the protein composition of secreted virions was largely unchanged.Interestingly, pp65 was not required for primary and persistent infection in animals.Immune responses induced by RhCMVΔpp65ab did not prevent reinfection withrhesus CMV; however, reinfection with RhCMVΔUS2-11, which lacks viral-encodedMHC-I antigen presentation inhibitors, was prevented. Unexpectedly, induction ofpp65b-specific T cells alone did not protect against RhCMVΔUS2-11 challenge,suggesting that T cells targeting multiple CMV antigens are required for protection.However, pp65-specific immunity was crucial for controlling viral disseminationduring primary infection, as indicated by the marked increase of RhCMVΔpp65abgenome copies in CMV-naive, but not CMV-immune, animals. Our data provide rationalefor inclusion of pp65 into CMV vaccines but also demonstrate that pp65-induced T cellresponses alone do not recapitulate the protective effect of natural infection.     

There is no "I" in team,but there is one in meeting

Increasingly, emotional intelligence (EI) and one's emotional quotient, or EQ, have become critical workforce success factors. This article examines the often overlooked issue of EI and EQ in group situations. It will delineate the three types of groups that show the most variance in emotional dynamics, and explore the application of EI and EQ to these group settings.     

A follow-up case study on teenage pregnancy: "havin' a baby isn't a nightmare, but it's really hard"

Two adolescent mothers who participated in a previously published study on teenage pregnancy agreed to participate in follow-up interviews in their homes about 1 1/2 years after giving birth. A naturalistic, qualitative case study approach was used to examine the participants' views and perceptions related to adolescent pregnancy and childbearing. Both mothers reported general satisfaction with their lives as young mothers, but indicated that their attitudes about early maternity changed once they experienced the day-to-day realities of motherhood. Overall, the participants adequately managed single motherhood with support from family. Regrets and hopes for a better future, mended and broken relationships, and thinking about and avoiding or engaging in fighting behavior were themes that emerged from the data. In addition, some of the findings of this case study were compared and contrasted with the initial study (Spear, 2001), and implications for practice and research are discussed.     

Early tumor dissemination,but late metastasis: insights into tumor dormancy

The classical model of metastasis is that tumor cell dissemination occurs late in tumor development, after the primary tumor has grown, and that only then will tumor cells invade the local tissue, enter the blood or lymphatic vessels, and colonize new sites to cause metastases. However, evidence increasingly indicates that single tumor cells spread to distant sites much earlier than previously believed. In this issue of the JCI, Eyles and colleagues provide new insight into the mechanisms underlying early tumor cell dissemination, formation of metastases, and tumor immunosurveillance using transgenic mice that spontaneously develop melanomas of the uvea. The authors provide striking evidence that tumor cells start to disseminate during the initial steps of tumor development, that late appearing metastases arise from these early disseminated tumor cells, and that CD8⁺ T cells inhibit the growth of disseminated tumor cells, surprisingly, not by cytotoxic effects, but through cytostatic effects.     

Yes, even human brown fat is on fire!

That adult humans possess brown fat is now accepted — but is the brown fat metabolically active? Does human brown fat actually combust fat to release heat? In this issue of the JCI, Ouellet et al. demonstrate that metabolism in brown fat really is increased when adult humans are exposed to cold. This boosts the possibility that calorie combustion in brown fat may be of significance for our metabolism and, correspondingly, that the absence of brown fat may increase our proneness to obesity — provided that brown fat becomes activated not only by cold but also through food-related stimuli. Brown adipose tissue is unique in possessing the ability to directly transfer energy from food into heat (1). This is due to the equally unique ability of its characteristic protein uncoupling protein 1 (UCP1) to allow for combustion of food energy in the brown fat mitochondria. Through this, brown fat produces heat for defense against cold — and may prevent obesity by allowing for combustion of energy, instead of storing the excess energy as fat. Brown adipose tissue has long been accepted as a metabolically important organ in small mammals (rats, mice), but only within the last five years has it been brought forward as a possibly metabolically significant tissue in adult humans. Anatomically, brown adipose tissue in adult humans is found primarily in depots in the neck and around the clavicles (Figure ​(Figure1).1). However, accepting the anatomical presence of the tissue is not the same as accepting that it plays an important metabolic role. Acceptance of brown adipose tissue as a significant factor in the metabolism of adult humans will be a stepwise process. Ouellet et al. (2) provide an important further step in this process. They demonstrate that brown adipose tissue in adult humans is actually metabolically highly active when it is stimulated physiologically, that is, even human brown fat is on fire. Open in a separate windowFigure 1Location and control of brown adipose tissue in adult humans.Brown adipose tissue (BAT) is mainly found in depots localized below the clavicles and in the neck (but amount and shape may vary considerably). The activity of the tissue is regulated from the brain, based on the need for heat for body temperature control (as investigated here by Ouellet et al.; ref. 2) (thermoregulatory thermogenesis) or also, probably, on the need for metaboloregulatory thermogenesis. The heat results initially from combustion of stored lipid within the brown adipose tissue (Figure ​(Figure2),2), but during prolonged thermogenesis, the components of ingested food are channeled to the tissue as a continuous supply of substrate.     

"It is very hard": treatment for childhood lymphoma from the parents' perspective

This article presents the findings of a five-year longitudinal study exploring the treatment experience for families coping with leukemia and lymphoma to address the dearth of psycho-social research documenting the experience of childhood lymphoma patients. The participants noted that the predominant differences for lymphoma families, as compared with other childhood hematological conditions, center around the issues of, firstly, the intensity of treatment. While the treatment protocol is comparatively shorter, the parents perceive it to be more arduous due to the intense and continuous nature of treatment. Important issues noted in this regard were the negative impact of the toxicity of the chemotherapeutic drugs, the stress associated with the invasiveness of accessing the child's veins for blood samples and to inject medications and the experience of undergoing lumbar punctures. Secondly, the relatively rare occurrence of pediatric lymphoma was reported to result in feelings of isolation from other families with children with a hematological malignancy and the unavailability of information and support services focusing specifically on childhood lymphoma. Thirdly, the relatively high curative success rate of lymphomas can have the effect that the parents feel that their angst is somewhat trivialized by other parents at the hospital. Recommendations include the importance of the availability of the full range of supportive care services, attention to the difficult emotional states the child patients experience, clinical strategies that lessen the trauma of treatment, and the use of positive role models by way of contact with or information of children who have successfully completed treatment.