Day: March 14, 2024

Scientists Find Weak Points on Epstein-Barr Virus

Photo by National Cancer Institute on Unsplash

Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. Study findings were published in the journal Immunity.

Approximately 95% of the world’s population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx.

EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers.

Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis.

There is no vaccine to prevent EBV infection nor a specific treatment.

In this study, investigators examined a viral protein called gp42, which the virus must use to infect B cells. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Theoretically, a vaccine or antibody-based treatment capable of blocking gp42’s ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus’s ability to persist in those cells.

The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42.

The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42.

Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion.

Next, the scientists tested A10, 4C12 and several other mAbs in mice for their ability to prevent EBV infection and EBV lymphomas.

The mAb A10 provided nearly complete protection against EBV infection and none of the mice developed lymphoproliferative disease or lymphoma.

In contrast, nearly all the mice treated with other mAbs became infected and some developed lymphoproliferative disease or lymphoma.

If future studies show mAb A10 to be safe and effective in humans, it could have clinical applications, particularly in people who have not been infected with EBV; those with immunodeficiency conditions, including severe combined immunodeficiency; or people receiving transplants.

People with such conditions are at risk of developing severe or fatal cases of EBV disease during their initial encounter with the virus.

The investigational monoclonal antibody could potentially be used prophylactically to prevent or better control EBV infections in such cases, the investigators note.

Additionally, the study team suggests that identification of the vulnerable sites on gp42 also paves the way to designing future vaccines that could elicit antibodies against one or both of the newly described sites.

Source: NIH/National Institute of Allergy and Infectious Diseases

Avid Appetite in Childhood Linked to Symptoms of Eating Disorder Later on

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An enthusiastic response to food in early childhood may be linked to a higher likelihood of experiencing eating disorder symptoms in adolescence, according to a new study led by researchers at UCL and Erasmus University Rotterdam.

The study, published inĀ The Lancet Child & Adolescent Health, looked at survey data from 3670 young people in the UK and the Netherlands to investigate how appetite traits in early childhood might relate to the likelihood of developing eating disorder symptoms up to 10 years later.

The team also found that a slower pace of eating and feeling full more quickly (high sensitivity to satiety) in early childhood may be protective against developing some eating disorder symptoms later.

Co-lead author Dr Ivonne Derks (UCL Institute of Epidemiology & Health Care) said: “Although our study cannot prove causality, our findings suggest food cue responsiveness may be one predisposing risk factor for the onset of eating disorder symptoms in adolescence.

“However, high responsiveness to food is also a normal and very common behaviour and should be seen as just one potential risk factor among many rather than something to cause parents worry.”

Higher food responsiveness was linked to a 16% to 47% increase in the odds of reporting eating disorder symptoms, including binge eating symptoms, uncontrolled eating, emotional eating, restrained eating and compensatory behaviours.

The 47% increase was found for binge eating symptoms (eating a very large amount of food and/or experiencing the feeling of loss of control over eating), meaning that adolescents whose parents rated them highest on food responsiveness were almost three times more likely to report binge eating symptoms compared to adolescents whose parents scored them lowest.

A 16% increase in odds was found for restrained eating, whereby a person restricts their intake of food to lose weight or avoid weight gain.

Just like food responsiveness, emotional overeating in early childhood was also linked with higher odds of engaging in compensatory behaviours, which are intended to avoid weight gain, such as skipping meals, fasting and excessive exercise.

In turn, some appetite traits seemed to be protective against developing eating disorder symptoms later. Higher satiety responsiveness ā€“ that is, feeling full more quickly after eating, and feeling full for longer ā€“ was linked to lower odds of uncontrolled eating (defined as the extent to which someone feels out of control and eats more than usual) and compensatory behaviours.

A slower pace of eating, meanwhile, was linked to lower odds of compensatory behaviours and restrained eating.

The researchers also found that appetite traits such as food fussiness, emotional undereating (eating less due to low mood), and enjoyment of food in early childhood were not linked to later eating disorder symptoms in adolescence.

For the study, the researchers looked at data from two separate longitudinal studies: Generation R, following children born in Rotterdam, the Netherlands, between 2002 and 2006, and Gemini, which follows twins born in England and Wales in 2007.

Appetite traits were assessed based on parents’ questionnaire responses when the children were aged four or five. Eating disorder symptoms were self-reported by the then adolescents themselves at ages 12 to 14, when eating disorder symptoms typically start to emerge.

About 10% of the adolescents reported binge eating symptoms, where people eat an unusual amount of food and/or experience the feeling of loss of control over eating. Next to that, 50% reported at least one behaviour to compensate their food intake or to avoid gaining weight, such as skipping a meal.

Co-senior author Dr Clare Llewellyn (UCL Institute of Epidemiology & Health Care) said: “While the role of appetite in the development of obesity has been studied for many decades, this is the first study to comprehensively examine the role of appetite traits in the development of eating disorder symptoms.

“Eating disorders can be harder to treat effectively once they develop and so it would be better to prevent them from occurring in the first place. Our work in identifying risk factors in early life aims to support the development of possible prevention strategies. These could, for instance, involve providing extra support to children at higher risk.”

Appetite traits are divided into food approach appetitive traits (eg, food responsiveness, enjoyment of food, emotional overeating) and food avoidance traits (eg, satiety responsiveness, food fussiness, slowness in eating, emotional undereating).

The researchers found that non-responsive feeding practices, such as putting pressure on children to eat or using food as a reward or to soothe emotions, were linked to a higher likelihood of specific eating disorder symptoms later. However, the associations were small and varied between the two cohorts, and the researchers said further replication studies were needed.

Source: University College London