Adenovirus 36 Research Articles

An Important Problem in AdV-36 Seropositive Obesity Patients: Leptin Resistance

Adenoviruses are naked viruses with an icosahedral nucleocapsid containing a 36 kb linear double-stranded DNA genome that encodes 30-40 proteins. The word "obesity" in Latin means "because of feeding". Obesity is an energy metabolism pathology that paves the way for physical and psychological problems with excessive fat accumulation that can impair health. Body mass index (BMI), unaffected by gender and age, is the most useful indicator of overweight and obesity at the population level. The concept of infectobesity was first introduced in 1978 after the data showed that viruses might also play a role in obesity cases. In the same year, adenovirus 36 (AdV-36) was isolated from the stool of a six-year-old girl with diabetes who was admitted to the hospital with the complaint of enteritis. One of the adipokines important for obesity is leptin. Leptin regulates food intake and energy metabolism by having a "negative feedback" effect on the hypothalamus. Leptin acts as a sensor that acutely regulates energy metabolism by creating hunger and satiety signals and it also regulates the amount of body fat and the required weight of the person by adjusting its concentration in the plasma according to the nutritional status. Changes in body weight and metabolic status are often associated with acute or chronic inflammatory processes. Human cells infected by AdV-36 showed greater differentiation and higher lipid accumulation than uninfected control cells, which increases the prevalence of obesity. There are two fractions of serum leptin, protein-bound and free form. The balance between these two fractions depends on serum leptin and soluble leptin receptor (sLR) plasma concentration, which is adversely affected by BMI. AdV-36 infection reduces norepinephrine and leptin levels. These two effects contribute to obesity by increasing appetite and food intake. In this study, it was aimed to determine the presence of immunoglobulin G against AdV-36 in the blood serum of obesity patients (BMI≥ 30) and healthy weight individuals (18.5≤ BMI≤ 25), and also aimed to determine and compare the leptin and soluble leptin receptor levels of these individuals. In this study, 10 ml of blood was collected on an empty stomach from obese individuals (n= 101; BMI≥ 30) and healthy individuals (n= 96; 18.5≤ BMI≤ 25) between the ages of 18-55. All participants consisted of who were not taking any medication and were not immunosuppressed. Blood samples separated into their serum were analyzed for AdV-36 IgG, leptin, and soluble leptin receptor levels. Mean, standard deviation, and percentage values were calculated by descriptive statistical analysis. The data with normal distribution were evaluated with the paired and independent sample t-test and data with abnormal distribution were evaluated with the paired and independent sample Mann-Whitney U test. Findings with a p-value less than 0.05 were considered statistically significant. In conclusion, leptin levels in obese individuals who were not infected with Adv-36 were found to be low, in line with the principle that "insufficient leptin synthesis has a role in the pathophysiology of obesity". When AdV-36 infection is added to the obesity picture, it may be due to the fact that it increases leptin synthesis in patients and the level of soluble leptin receptors increases in response to the increased leptin level, that AdV-36 suppresses the binding of the leptin molecule to its receptor, which leads to leptin resistance.

Inflammatory cytokines and chemokines in obese adolescents with antibody against to adenovirus 36

Obesity in adolescents has reached epidemic proportions and is associated with the inflammatory response and viral infections. The aim of this study was to understand the profile of inflammatory cytokines and chemokines associated with the inflammatory response and metabolic syndrome (MetS) in obese adolescents with positive serology for adenovirus 36 (ADV36). Thirty-six overweight, 36 obese, and 25 severe obesity adolescents aged 10 to 16 years were included in the study. The following variables were analyzed: sex, age, body mass index (BMI), blood pressure, total cholesterol and fractions, triglycerides, glucose, serum cytokine concentrations, and ADV36 antibodies. Cytokines and chemokines were quantified by cytometry and ADV36 serology was determined by enzyme-linked immunosorbent assay (ELISA). The results showed higher levels of the cytokines interleukin-1beta (IL-1β), IL-6, IL-10 and of the chemokine interferon-gamma-inducible protein 10 (IP-10) in severe obesity adolescents compared to the obese and overweight groups, as well as in the group with MetS compared to the group without this syndrome. The frequency of ADV36-positive individuals did not differ between groups. The findings revealed differences in BMI between the obese and severe obesity groups versus the overweight group in the presence of positivity for ADV36, suggesting an association with weight gain and possibly MetS installation.

Long-term infection passaging of Human Adenovirus 36 in monkey kidney cells

Human Adenovirus 36 (HAdV-36) has been related to diverse effects on metabolism and may attenuate the lipid accumulation in kidneys with increased adiposity. Some of these effects would be related to viral persistence. However, until now, a model of persistent in vitro infection by HAdV-36 is unknown. In this study, we examined the cells of the Vero lineage to explore their permissiveness to long-term HAdV-36 infection. HAdV-36 was productively replicated in Vero cells and maintained long-term infection for up to 35 cell passages. A subculture was obtained from the cells that survived the primary infection at a low MOI (0.5). The production of the extracellular infectious virus with titers ranging from 104 to 106 TCID50/mL and DNA-bearing cells was detected. In long-term infected cells, the intracellular distribution of viral antigen was demonstrated by performing immunolocalization (IFI) and expression of cell-viral antigen in 50% of cells by flow cytometry, using anti-HAdV-36 hyperimmune rabbit serum. Furthermore, E1a and E4orf1 genes in long-term infected passages showed a decreasing trend. Our preliminary results reveal that renal epithelial monkey cells are permissive for the productive infection of HAdV-36. Vero cell culture long-term infection might be a promising model for addressing the fundamental aspects of the HAdV-36 biology that cannot reveal broadly-used cultures, which do not maintain long-term infection in primary or transformed cells.

Presence of Adenovirus-36 DNA in Adipose Tissue of Women: Relationship with Adipocyte Morphology and the Expression of C/EBPβ and HIF-1α.

BackgroundHuman adenovirus 36 (HAd36) infection has been associated with obesity. Experiments using 3T3-L1 adipocyte cultured cells and human adipose stem cells (hASCc) have shown that HAd36 stimulates the expression of genes implicated in cell differentiation and increased lipid accumulation. The presence of HAd36 in adipose tissue of overweight and obese women has also been confirmed. This study aims to analyze the presence of HAd36 DNA in the adipose tissue of women undergoing surgery for weight reduction and its relationship with obesity through changes in adipocyte morphology as well as the expression of C/EBPβ and HIF-1α.MethodsFifty-two subcutaneous adipose tissue biopsies were collected. The anthropometric parameters measured were weight, height, skin folds, body circumferences, and body fat percentage. Biochemical measures were performed for glucose, cholesterol, triglycerides, cholesterol HDL-c, and LDL-c. The presence of HAd36 DNA was performed by conventional PCR. Adipocyte morphology was analyzed in H&E-stained sections using ImageJ/Fiji software. The expression of genes C/EBPβ, HIF-1α and β-actin was determined using TaqMan probes.ResultsHAd36 DNA was detected in 31% of adipose tissue samples. The presence of viral DNA was not significantly associated with anthropometric, clinical, or metabolic measurements, or with changes in adipose tissue morphology. The levels of mRNA expression for C/EBPβ and HIF-1α did not show significant differences between positive and negative samples for HAd36 (p>0.05).ConclusionThe presence of HAd36 DNA in adipose tissue was identified, but it was not related to morphological changes of adipocytes, or the expression of C/EBPβ and HIF-1α. Further studies are needed to confirm these findings.

Antiviral, Antibacterial, Antifungal, and Cytotoxic Silver(I) BioMOF Assembled from 1,3,5-Triaza-7-Phoshaadamantane and Pyromellitic Acid.

The present study reports the synthesis, characterization, and crystal structure of a novel bioactive metal-organic framework, [Ag4(µ-PTA)2(µ3-PTA)2(µ4-pma)(H2O)2]n·6nH2O (bioMOF 1), which was assembled from silver(I) oxide, 1,3,5-triaza-7-phosphaadamantane (PTA), and pyromellitic acid (H4pma). This product was isolated as a stable microcrystalline solid and characterized by standard methods, including elemental analysis, 1H and 31P{1H} NMR and FTIR spectroscopy, and single crystal X-ray diffraction. The crystal structure of 1 disclosed a very complex ribbon-pillared 3D metal-organic framework driven by three different types of bridging ligands (µ-PTA, µ3-PTA, and µ4-pma4−). Various bioactivity characteristics of bioMOF 1 were investigated, revealing that this compound acts as a potent antimicrobial against pathogenic strains of standard Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria, as well as a yeast (Candida albicans). Further, 1 showed significant antiviral activity against human adenovirus 36 (HAdV-36). Finally, bioMOF 1 revealed high cytotoxicity toward an abnormal epithelioid cervix carcinoma (HeLa) cell line with low toxicity toward a normal human dermal fibroblast (NHDF) cell line. This study not only broadens the family of PTA-based coordination polymers but also highlights their promising multifaceted bioactivity.

Obesity and Adenovirus 36: A Possible correlation?

Future VirologyVol. 15, No. 3 EditorialObesity and adenovirus 36: a possible correlation?Carmine FinelliCarmine Finelli*Author for correspondence: E-mail Address: carminefinelli74@yahoo.itDepartment of Internal Medicine, Ospedale Cav. R. Apicella – ASL Napoli 3 Sud, Via di Massa, 1, 80040 Pollena, Napoli, ItalySearch for more papers by this authorPublished Online:8 Apr 2020https://doi.org/10.2217/fvl-2019-0098AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: adenovirus 36adipogenesisE4orf1 proteininfectious diseaseinfectobesityobesity

The relationship between human adenovirus 36 and obesity in Chinese Han population.

The study aimed to explore the prevalence of human adenovirus-36 (HAdV-36) infection and the association of HAdV-36 with obesity in Chinese Han population. A qualitative determination using ELISA was performed to determine by duplication of the antibodies to HAdV-36 in the serum samples. Logistic regression analysis was used to analyze the association between HAdV-36 seropositivity and obesity. The overall HAdV-36 seroprevalence was 49.8% amongst 824 participants. The prevalence of HAdV-36 seropositive was 42.9 and 51.4% in the obese and non-obese participants, respectively, which was not statistically significant (P=0.05). There were significant differences in the anthropometric and biochemical parameters observed between the two groups except for height (P=0.067) and total cholesterol (TC) (P<0.29). After the adjustment for age and gender, HAdV-36 seropositivity was a protective factor for obesity (odds ratio (OR) = 0.69, 95% confidence intervals (95% CI) = 0.48–0.97, P=0.03). In the male population, the adjusted OR for AD-36 antibody-positive status was statistically decreased for obese adults (OR = 0.59; 95% CI = 0.39–0.91; P=0.02). However, the similar result was not obtained in the female population (OR = 0.90; 95% CI = 0.48–1.67; P=0.73). We found a high prevalence of HAdV-36 infection in China and significant association between HAdV-36 infection and obesity or weight gain after the adjustment for age and gender. The HAdV-36 infection may be related to the weight loss in Chinese Han population, especially in the male group, which needs to be further confirmed.

‘Infectobesity’ in egyptian adolescent women and its relations to carotid intima–media thickness

Background ‘Infectobesity’ is a new term to describe obesity of infectious origin, such as infection by human adenovirus-36 (Adv36). It appears to be a new concept, evolved over the past 20 years. Visceral obesity is associated with a higher risk of cardiovascular disease. Increased carotid intima–media thickness (CIMT), a marker of early-onset atherosclerosis, has been observed in obese children and adolescents. The present study aims to investigate the relationship between visceral obesity, CIMT, and Adv36 in female Egyptian adolescents. Patients and methods The present study included 90 women aged 12–15 years. It was conducted at the Medical Excellence Research Center of the National Research Centre, Cairo, Egypt, during the period between September 2016 and November 2017. Anthropometric assessment was done. Fasting blood samples were withdrawn for the measurement of Qualitative Human Adv36 antibody using a sandwich enzyme-linked immunosorbent assay. Fasting plasma glucose was determined calorimetrically, by the glucose oxidase method and insulin level using the solid-phase enzyme-linked immunosorbent assay and lipid profile. Visceral obesity was measured by an abdominal ultrasound. CIMT for both carotid arteries were measured by high-resolution echo Doppler. Results Girls with visceral obesity (n=26) had higher frequency of increased CIMT at left (96.2 vs. 75%), right carotid artery (84.6 vs. 73.4%) and Adv36 sero-positive antibody (69.2 vs. 56.2%) than among those without visceral obesity (n=64). Among the total samples, visceral obesity had significant positive correlations with BMI, waist and hip circumference, while it had insignificant correlations with age, blood pressure (BP), CIMT at right and left carotid arteries, adenovirus and laboratory findings. CIMT had a significant positive correlation with each other, insulin resistance and total cholesterol, and significant negative correlations with high-density lipoprotein and waist circumference. Adv36 had significant negative correlations with BP (both systolic and diastolic) and significant positive correlation with insulin level. Adv36 and CIMT had insignificant correlations with each other and with the anthropometric measurements, BP, visceral obesity, triglycerides, and low density lipoprotein. Conclusion The frequency of Adv36 and increased CIMT at left carotid artery were higher among girls with visceral obesity than among those without visceral obesity. However, visceral obesity, CIMT at both right and left carotid arteries, and Adv36 had insignificant correlations with each other.

Human adenovirus-36 seropositivity and obesity among Midwestern US adolescents.

Objective Human adenovirus-36 (Ad-36) infection has been implicated as a risk factor for obesity. This study aims to measure Ad-36 antibody prevalence among obese and healthy-weight Midwestern US adolescents. Methods Obese and healthy-weight subjects 10-18 years of age attending an adolescent clinic in Missouri, USA, were tested for Ad-36 antibodies via ELISA assay. All subjects were measured for height and weight to determine body mass index (BMI). χ2 analysis was used to compare Ad-36 antibody prevalence between the two groups. Results Ad-36 antibodies were tested on 41 obese and 37 control subjects. The subjects' mean age at the time of sample collection was 15.6 years (SD 2.0). Ad-36 antibody prevalence was 43.9% among the obese group and 21.6% among the control group (p = 0.038). Discussion The findings show that statistically more obese Missouri adolescents test positive for Ad-36 antibodies than their healthy-weight peers, consistent with previous findings suggesting a correlation between Ad-36 infection and obesity.

Adenovirus 36 antibody detection: Improving the standard serum neutralization assay

Adenovirus 36 (AdV36) causes weight gain in animal models, including non-human primates. In humans, AdV36-neutralizing antibodies are associated with adiposity; however, longitudinal studies in large populations are needed to clarify AdV36′s contribution. The current gold standard for detection of AdV36-specific antibody is the serum neutralization assay (SNA), which requires long incubation times and highly trained personnel. The standard SNA was modified using an immunocytochemical (ICC) approach, which allows for a more rapid and objective assessment of AdV36 antibodies. Using the ICC assay, virus-infected cells were detected as early as day 1 (D1) and by D5 were detected in 100% of microtiter wells versus 20.3% of wells detected by observing the cytopathic effect. Further, human sera tested with the ICC assay at D5 had a sensitivity and specificity of 80.0% and 95.7%, respectively, when compared to the standard SNA read at D11. Thus, the ICC assay decreased assay incubation time, provided a more objective and easily interpreted assessment, and had a high degree of sensitivity and specificity in determining serological status. The more rapid and objective ICC method will make large population studies feasible, improve comparability among laboratories, and contribute to understanding the role of AdV36 in obesity.

Association between human adenovirus-36 infection, obesity and glycemia in prospective follow-up of Hong Kong Chinese school children

Association between human adenovirus-36 infection, obesity and glycemia in prospective follow-up of Hong Kong Chinese school children

Human Adenovirus 36 Infection Increased the Risk of Obesity: A Meta-Analysis Update.

Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses.We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed.Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P < 0.001) with a high heterogeneity (I = 80.1%; P < 0.001) estimated by the random effect model. Subgroup analysis demonstrated that the pooled OR of HAdV-36 infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P < 0.001) in the adults and children, respectively. Compared to the HAdV-36 negative subjects, the SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: -0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I = 86.5%; P < 0.001). The BMI z-score in the children with HAdV-36 infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: -0.31, 0.70; PI: -2.10, 2.49), which had no significantly statistical difference (P = 0.453).HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children.

Association of Human Adenovirus-36 With Dyslipidemia in Tehranian Children and Adolescent; TLGS

Background: The human adenovirus-36 (Adv36) has been associated with obesity and lipid disorders in some countries. The primary dyslipidemia related to obesity is characterized by increased TG, decreased HDL levels and abnormal LDL composition. Childhood obesity is a major public health problem in most developing countries. Objectives: The aim of this study was to investigate the association between Adv36 and lipid disorders in Tehranian youth. Patients and Methods: In a cross-section/observational study, anthropometric, blood pressure and biochemical measurements were examined in 54 youth, aged below 19 years, selected randomly from participants of Tehran Lipid and Glucose Study (TLGS) of Iran. Human Adv36 antibody of serum was determined using ELISA method. Results: Of 54 youth, with a mean age of 14.78 ± 2.62 years, 85.2% were Adv36 seropositive (N = 46) and 14.8% were seronegative (N = 8). Subjects with Adv36 seropositive had higher mean of age, weight, TC, LDL-C, TG and SBP and lower level of HDL-C, waist, FBS and DBP. The unadjusted OR for elevated TG increased in participants who were Adv36 seropositive (OR 3.062, 95% CI: 0.344-27.293). Although the unadjusted OR for other lipid variables, such as elevated TC and LDL-C or decreased HDL-C, tended to increase in participants who were Adv36 seropositive (OR 1.028, 95% CI: 0.996 - 1.060; OR 1.057, 95% CI: 0.107 - 10.481; OR 1.125, 95% CI: 0.238 - 5.325, respectively), the results were not significant. Conclusions: It seems that seropositive Adv36 has a strong association with lipid disorders, especially elevated TG level in Tehranian children and adolescent.

The role of adenovirus 36 as a risk factor in obesity: The first clinical study made in the fatty tissues of adults in Turkey

Obesity which developes due to multifactorial reasons, was associated recently with human Adenovirus-36 (Ad-36). The aim of this study was to investigate the prevalence of Ad-36 antibodies in obese adults and also to investigate the DNA of Ad-36 in their adipose tissue. In this cross-sectional and case-control based study, 49 obese adults, with BMI ≥30 kg/m2, and 49 non-obese adults, with BMI ≤25 kg/m2, applied for esthetic purposes and were included in this study as patient and control groups, respectively. Adipose tissue samples, obtained by the lipoaspiration method, were studied by single-step PCR and nested-PCR methods. Simultaneously, the presence of Ad-36 antibodies and serum leptin and adiponectin levels were assessed by serum neutralization assay (SNA) and ELISA, respectively. Serum samples which didn't cause a cytopathic effect at ≥1:8 were accepted as positive. Ad-36 antibody was detected in 6 (12.2%) of 49 patients by SNA and was statistically significant (p < 0.05). Ad-36 DNA was not detected in any of the adipose tissue samples of the patient or control groups. Mean BMI and leptin levels were higher in the Ad-36-positive group, while adiponectin levels were found to be lower in the Ad-36-positive group. Although no statistically significant difference was found in cholesterol and triglyceride levels between the two groups (p > 0.05), lower mean serum cholesterol and triglyceride levels were found in the Ad-36-positive patients. In conclusion, we couldn't detect Ad-36 DNA in adipose tissue; however, we detected significantly higher Ad-36 antibody levels in the obese group compared to the non-obese group, according to the both univariant and multivariant analyses, suggesting that Ad-36 may play a role in obesity. There is a need for new and extended serial, particularly cohort and human-based, studies in order to have a clear understanding of the Ad-36-obesity relationship.

Human adenovirus-36 is uncommon in type 2 diabetes and is associated with increased insulin sensitivity in adults in Sweden

Background. Human adenovirus-36 (Adv36) increases adiposity, but also upregulates distal insulin signaling in vitro in human adipose and muscle tissue and in vivo in the rodent independently of adiposity. Accordingly, healthy adults and children with antibodies against Adv36 had increased insulin sensitivity and reduced hepatic lipid accumulation. We hypothesized that Adv36 infection would be less frequent in individuals with type 2 diabetes or impaired glycemic control.Methods. Presence of antibodies against Adv36 was analyzed for association to type 2 diabetes or impaired glycemic control in a two-wave population-based sample of well-characterized adults (n = 1734). Indices of impaired glycemic control included oral glucose tolerance, and circulating fasting levels of glucose, insulin, and insulin-like growth factor binding protein-1 (IGFBP-1).Results. Adv36 seropositivity was more common in those with normal glucose tolerance (NGT) than in those with diabetes (females: OR 17.2, 95% CI 4.0–74.3; males: OR 3.5, 95% CI 1.8–6.7). Also, females with NGT had higher frequency of Adv36 seropositivity than females with prediabetes (impaired glucose tolerance and/or impaired fasting glucose; OR 1.8, 95% CI 1.1–3.1). Within the female prediabetes group Adv36 seropositivity was associated with higher insulin sensitivity reflected by reduced HOMA-IR and increased IGFBP-1.Conclusion. Adv36 infection is associated with lower occurrence of type 2 diabetes and better insulin sensitivity in adults, particularly among females.

Adenovirus-36 prevalence paradox in development

For decades, adenovirus-36 (AD-36) and infectobesity are part f an ongoing discussion within obesity research based on intrigung results described first in 1992 in animals by Dhurandhar et al.1 nd in 2005 in humans by Atkinson et al.2 Recently, this topic is ntroduced also in clinical virology by Esposito et al.3 Within this linical virological view, the authors indicate that available data including molecular results in animals and serological results n USA, Korea and Italy with AD-seroprevalences up to 30% and igher – do not completely solve the problem of the possible relaionship between AD-36 infection and obesity in humans.3 For erological results, as in the previous literature the authors indicate hat AD-36 is distinct from all other human adenoviruses in terms f neutralization and hemagglutination inhibition, and does not ross-react with other viruses.3 Besides molecular results in anials, also limited results in humans are available although maybe n a paradoxal way. Therefore we want to comment on the indicated pecificity of AD-36 serology and on a non-neglectable absence or on-detection of AD-36 in most adenoviral studies in humans. Few positive reports for AD-36 culture and/or PCR are available ince the isolation of the original AD-36 strain in 1978.4 In 2008, asarica and coworkers including Dhurandhar, described natural D-36 infection in 9 obese, normoglycemic Native American Pima ndians by PCR on subcutaneous abdominal adipose tissue.5 In 010, Salehian and coworkers including Atkinson, described the etection of AD-36 DNA in a patient with unusual visceral obesity.6 emarkable, as a control, samples of adipose tissue obtained by eedle fat biopsy from 12 obese persons without abnormal adiose tissue deposits were positive also. According to the authors, he prevalence of AD-36 infection identified by PCR was similar to hat identified by serum neutralization in obese adults in the United tates.6

Adenovirus-36 is associated with obesity in children and adults in Sweden as determined by rapid ELISA.

BackgroundExperimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals.Principal FindingsUsing a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 non-diabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from ∼7% in 1992–1998 to 15–20% in 2002–2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08).ConclusionUsing a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.

Adenovirus‐36 and obesity

Adenovirus‐36 and obesity

Response to ‘human adenovirus‐36 and childhood obesity’

Response to ‘human adenovirus‐36 and childhood obesity’

Human adenovirus-36 and childhood obesity

There is increasing evidence that obesity in humans is associated with infection with human adenovirus-36 (Adv36). Infection of experimental animals with Adv36 demonstrates that this virus causes obesity. Human studies have shown a prevalence of Adv36 infection of 30% or greater in obese adult humans, but a correlation with obesity has not always been demonstrated. In contrast, three published studies and one presented study with a total of 559 children all show that there is an increase in prevalence of Adv36 infection in obese children (28%) compared to non-obese children (10%). The explanation for the apparently more robust correlation of Adv36 infection with obesity in children vs. adults is not clear. The data in animals and people suggests that Adv36 has contributed to the worldwide increase in childhood obesity. More research is needed to identify prevalences and consequences of Adv36 infection in people of all age groups and geographic locations.