Canine picornaviruses detected in wastewater in Arizona, USA 2019 and 2021.

Virus surveillance by wastewater-based epidemiology (WBE) in two Arizona municipalities in Maricopa County, USA (~700,000 people), revealed the presence of six canine picornavirus (CanPV) variants: five in 2019 and one in 2021. Phylogenetic analysis suggests these viruses might be from domestic dog breeds living within or around the area. Phylogenetic and pairwise identity analyses suggest over 15 years of likely enzootic circulation of multiple lineages of CanPV in the USA and possibly globally. Considering <10 CanPV sequences are publicly available in GenBank as of June 2, 2022, the results provided here constitute an increase of current knowledge on CanPV diversity and highlight the need for increased surveillance.

Dynamic Changes in Breast Milk Microbiome in the Early Postpartum Period of Kenyan Women Living with HIV Are Influenced by Antibiotics but Not Antiretrovirals.

Shared bacteria between maternal breast milk and infant stool, infers that transfer of maternal breast milk microbiota through breastfeeding seeds the establishment of the infant gut microbiome. Whether combination antiretroviral therapy (cART) impacts the breast milk microbiota in women living with HIV is unknown. Since current standard of care for people living with HIV includes cART, it has been difficult to evaluate the impact of cART on the microbiome. Here, we performed a next-generation sequencing retrospective study from pre-ART era clinical trials in Nairobi, Kenya (between 2003-2006 before cART was standard of care) that tested the effects of ART regimens to prevent mother-to-child HIV transmission. Kenyan women living with HIV were randomized to receive either no ART during breastfeeding (n = 24) or cART (zidovudine, nevirapine, lamivudine; n = 25) postpartum. Using linear mixed-effects models, we found that alpha diversity and beta diversity of the breast milk bacterial microbiome changed significantly over time during the first 4 weeks postpartum (alpha diversity P < 0.0007; beta diversity P = 0.005). There was no statistically significant difference in diversity, richness, and composition of the bacterial microbiome between cART-exposed and cART-unexposed women. In contrast, antibiotic use influenced the change of beta diversity of the bacterial microbiome over time. Our results indicate that while early postpartum time predicts breast milk microbiome composition, cART does not substantially alter the breast milk microbiota in women living with HIV. Hence, cART has minimal impact on the breast milk microbiome compared to antibiotics use. IMPORTANCE Breastfeeding has important benefits for long-term infant health, particularly in establishing and shaping the infant gut microbiome. However, the impact of combination antiretroviral therapy exposure and antibiotics on the breast milk microbiome in women living with HIV is not known. Here, in a longitudinal retrospective study of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that antibiotic use significantly influenced breast milk microbiome beta diversity, but antiretrovirals exposure did not substantially alter the microbiome. Given the protective role of breastfeeding in maternal-infant health, these findings fill an important knowledge gap of the impact of combination antiretroviral therapy on the microbiome of women living with HIV.

Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition.

While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Laniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171-180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123-137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women's health. IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women's health.

Genomic Sequencing of SARS-CoV-2 E484K Variant B.1.243.1, Arizona, USA.

Genomic surveillance can provide early insights into new circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. While conducting genomic surveillance (1,663 cases) from December 2020-April 2021 in Arizona, USA, we detected an emergent E484K-harboring variant, B.1.243.1. This finding demonstrates the importance of real-time SARS-CoV-2 surveillance to better inform public health responses.

Andrographolide Attenuates Gut-Brain-Axis Associated Pathology in Gulf War Illness by Modulating Bacteriome-Virome Associated Inflammation and Microglia-Neuron Proinflammatory Crosstalk.

Gulf War Illness (GWI) is a chronic multi-symptomatic illness that is associated with fatigue, pain, cognitive deficits, and gastrointestinal disturbances and presents a significant challenge to treat in clinics. Our previous studies show a role of an altered Gut-Brain axis pathology in disease development and symptom persistence in GWI. The present study utilizes a mouse model of GWI to study the role of a labdane diterpenoid andrographolide (AG) to attenuate the Gut-Brain axis-linked pathology. Results showed that AG treatment in mice (100 mg/kg) via oral gavage restored bacteriome alterations, significantly increased probiotic bacteria Akkermansia, Lachnospiraceae, and Bifidobacterium, the genera that are known to aid in preserving gut and immune health. AG also corrected an altered virome with significant decreases in virome families Siphoviridae and Myoviridae known to be associated with gastrointestinal pathology. AG treatment significantly restored tight junction proteins that correlated well with decreased intestinal proinflammatory mediators IL-1ß and IL-6 release. AG treatment could restore Claudin-5 levels, crucial for maintaining the BBB integrity. Notably, AG could decrease microglial activation and increase neurotrophic factor BDNF, the key to neurogenesis. Mechanistically, microglial conditioned medium generated from IL-6 stimulation with or without AG in a concentration similar to circulating levels found in the GWI mouse model and co-incubated with neuronal cells in vitro, decreased Tau phosphorylation and neuronal apoptosis. In conclusion, we show that AG treatment mitigated the Gut-Brain-Axis associated pathology in GWI and may be considered as a potential therapeutic avenue for the much-needed bench to bedside strategies in GWI.