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An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

Petroleum crude oil spills are common and vary in size and scope. Spill response workers throughout the course of remediation are exposed to so-called weathered oil and are known to report diverse health effects, including contact dermatitis. A murine model of repeated exposure to weathered marine crude oil was employed utilizing two strains of mice, C57BL/6 and BALB/c, to investigate the pathology of this irritant and identify the principal hydrocarbon components deposited in skin. Histopathology demonstrated clear signs of irritation in oil-exposed skin from both mouse strains, characterized by prominent epidermal hyperplasia (acanthosis). BALB/c mice exposed to oil demonstrated more pronounced irritation compared with C57BL/6 mice, which was characterized by increased acanthosis as well as increased inflammatory cytokine/chemokine protein expression of IL-1β, IL-6, CXCL10, CCL2, CCL3, CCL4, and CCL11. A gas chromatography/mass spectrometry method was developed for the identification and quantification of 42 aliphatic and EPA priority aromatic hydrocarbons from full thickness skin samples of C57BL/6 and BALB/c mice exposed to oil samples. Aromatic hydrocarbons were not detected in skin; however, aliphatic hydrocarbons in skin tended to accumulate with carbon numbers greater than C16. These preliminary data and observations suggest that weathered crude oil is a skin irritant and this may be related to specific hydrocarbon components, although immune phenotype appears to impact skin response as well.

OBJECTIVE Two distinct hypotheses have been proposed for T-cell involvement in protection from HIV-1 acquisition. First, HIV-1-specific memory T-cell responses generated on HIV-1 exposure could mount an efficient response to HIV-1 and inhibit the establishment of an infection. Second, a lower level of immune activation could reduce the numbers of activated, HIV-1-susceptible CD4 T cells, thereby diminishing the likelihood of infection. METHODS To test these hypotheses, we conducted a prospective study among high-risk heterosexual men and women, and tested peripheral blood samples from individuals who subsequently acquired HIV-1 during follow-up (cases) and from a subset of those who remained HIV-1 uninfected (controls). RESULTS We found no difference in HIV-1-specific immune responses between cases and controls, but Treg frequency was higher in controls as compared with cases and was negatively associated with frequency of effector memory CD4 T cells. CONCLUSIONS Our findings support the hypothesis that low immune activation assists in protection from HIV-1 infection.

More than 30 years into the global human immunodeficiency virus (HIV) epidemic, novel HIV prevention strategies are still being sought, particularly interventions that would reduce HIV susceptibility and impart long-term immune protection. Four randomized, placebo-controlled clinical trials, conducted among diverse geographic and at-risk populations, demonstrated that HIV-uninfected persons taking a daily oral antiretroviral as preexposure prophylaxis (PrEP), tenofovir either alone or coformulated with emtricitabine, are at substantially reduced risk of HIV acquisition [1–4]. Although the primary mechanism of protection afforded by PrEP is thought to be through direct antiviral activity, it has been hypothesized that, by blocking initial viral replication, PrEP might permit enhanced presentation of HIV to the immune system and the subsequent development of HIV-specific adaptive immune responses. This hypothesis has been supported by 2 nonhuman primate studies, which reported the presence of HIV-specific T-cell responses in a majority of animals that received PrEP before virus exposure [5, 6]. The potential effect of PrEP on the development of HIV-specific immune responses in humans has not been explored but is a priority question as PrEP is implemented. Efficacy trials of prophylactic HIV vaccines enroll subjects at high risk of HIV acquisition and provide a package of effective prevention services, which will probably include PrEP in future trials. Thus, the question of whether PrEP modifies immune responses is particularly significant, because preexisting or “natural” immunity could alter the efficacy of the vaccine. Given the potential for PrEP to support selection of HIV-specific immune responses, as well as to influence the outcomes of immune responses to HIV vaccines, we assessed whether PrEP allows for enhanced development of HIV-specific T cells among 247 HIV-seronegative partners in HIV-serodiscordant couples participating in an efficacy trial of PrEP for HIV prevention. Randomization to PrEP or placebo in the trial permitted a direct comparison of the effect of PrEP on inducing HIV-specific CD4+ and CD8+ T-cell and natural killer (NK) cell responses in these HIV-1–exposed seronegative (HESN) individuals. Furthermore, we extensively characterized T-cell, NK cell, and dendritic cell (DC) phenotypes to evaluate whether their frequency, activation, or maturation status were modified by PrEP. Our study, conducted on a large cohort of subjects selected for their high exposure to HIV, provides an extensive characterization of the effects of PrEP on HIV-specific immunity.