Abstract Biological sex is a significant determinant of host responses and disease outcomes during viral infection. Although males often exhibit more robust pathological inflammatory responses, the implications for immune responses within the central nervous system remain unclear. Given that many viral infections can lead to long-term neurological complications, it is crucial to understand how biological sex influences neuroinflammation. Using a mouse model of Zika virus infection, we find that males develop more severe clinical disease compared to females, despite comparable infectious viral loads. Our findings demonstrate that sexually dimorphic immune responses contribute to increased male susceptibility to virus-induced neuropathology.
Abstract To describe seasonal patterns of respiratory viruses in infants presenting to primary care (PC) after the rollout of the RSV-immunisation programme in Spain, we analysed multiplex RT-PCR results from infants <1 year with lower respiratory tract infections (LRTIs) attending 57 PC centres in Valencia and Murcia across two seasons. Among the 307 infants, rhinovirus/enterovirus and RSV were the most common detections in both periods. hMPV, bocavirus, and influenza followed. Our findings highlight the importance of community-based surveillance systems for providing real-world evidence to inform future immunisation strategies.
Abstract Despite antiretroviral therapy, the latent viral reservoir (LVR) remains the primary barrier to human immunodeficiency virus (HIV) cure. Both hematopoietic and solid organ transplantation (SOT) have provided optimism for cure and significant insights into LVR composition and maintenance. There have been 13 reported cases of acquired cure, all in individuals receiving allogeneic hematopoietic stem cell transplants (allo-HSCT). While infeasible for most, these cases have provided important lessons about the LVR. Impacts of SOT on the LVR have also been investigated. In kidney transplantation where recipients were T-cell depleted, the LVR initially decreased before rebounding and eventually surpassed the LVR of recipients without T-cell depletion. Despite transplanting a large lymphoid organ, studies have found no impact of HIV+ liver transplants on LVR size in recipients. Given that SOTs are more accessible globally than allo-HSCTs, lessons learned about the LVR from these studies can inform potential cure avenues that may be more feasible and attainable.
BACKGROUND Streptococcus pneumoniae (Spn) infections are preceded by nasal colonization. By conferring protection against nasopharyngeal carriage, pneumococcal conjugate vaccines have reduced the global incidence of disease. Our understanding of vaccine-induced mechanisms of protection is aided by the Experimental Human Pneumococcal Challenge (EHPC) model, where healthy adult volunteers receive live Spn nasal inoculation. Here we evaluated the accumulation of Spn genetic diversity in the context of 13-valent pneumococcal conjugate vaccine (PCV13) immunization. METHODS We compared single nucleotide polymorphisms (SNPs), insertions/deletions (INDELs), and pangenome elements in Spn strains isolated from EHPC participants who received PCV13 (n=5) to those who received the control hepatitis A vaccine (n=10). This required whole genome sequencing the 45 Spn strains spanning nasal wash samples that occurred at days 2, 7, 14 and 21/22 post-vaccination and the serotype 6B Spn inoculum. RESULTS There was no difference in number of variants or genome size over time between Spn strains from the PCV13 and control groups. The most prevalent genetic variants were identified in both groups and the PCV13 group accessory genome content was inclusive of that of the control. Across arms, variance in pangenome elements largely related to transposons. CONCLUSIONS While genomic variation was observed between the groups, mutations or acquisition of genes directly related to pathogenesis was not associated with exposure to PCV13 over the course of the study period. This suggests that PCV13 does not drive short-term selection for vaccine-escape during colonization, but longer-term studies are needed to assess potential delayed effects or impact on non-vaccine serotypes.
BACKGROUND Cryptosporidium spp. are enteric protozoa associated with moderate-to-severe diarrhea and impaired growth in children worldwide. However, the relationship between Cryptosporidium infection and gut microbiome remains poorly understood. METHODS We investigated gut microbiota dynamics associated with Cryptosporidium infection in a longitudinal cohort of 84 children and family members in Bangladesh. Fecal samples (n=233) were collected pre-infection, during infection, and post-infection. Microbial profiling was performed using 16S rRNA sequencing, with taxonomic classification and abundance estimation conducted via Cosmos ID-HUB. Associations between infection status, microbial diversity, and taxa abundance were evaluated using multivariable models adjusting for age and sex. RESULTS Most Cryptosporidium infections were subclinical (96.1%), with 3.86% presenting diarrhea. In individuals ≥ 3 years of age, gut microbial α-diversity decreased during infection (p-value range = 0.01-3.68x10-10) and increased following recovery (p-value range = 0.0017- 0.0019). During infection, Roseburia and Megaspheara were reduced relative to both pre- (q-value = 0.011 and 0.02) and post-infection (q-value =2.34 x10-5 and 0.001). In addition, Prevotella (q-value = 0.03) and Leuconostoc (q-value=0.04) were reduced relative to pre-infection. Shigella abundance increased during infection (q-value =3.4x10-5) and persisted post-infection (q-value=9.0x10-6). In children ≤ 3 years of age, α-diversity increased during infection compared to pre-infection (p-value=0.045). α-diversity and β-diversity during the post-infection period were associated with lower weight for age z scores. CONCLUSIONS Cryptosporidium infection is associated with dynamic and persistent alterations in the gut microbiome, even in the absence of diarrhea, which may be related to impaired child growth, and deserve deeper analysis as promising potential targets for microbiota-mediated interventions.
