Flu pandemics: homeopathic prophylaxis and definition of the epidemic genius

Recent studies on viral genetics establish swine-H1N1 – responsible for the ongoing pandemics – as a remainder or continuation of the agent causing the flu epidemics of 1918. This study aimed at analyzing whether this common etiology also result in significant correlations of clinical manifestations. To do so, data were collected to compare the clinical evolution of cases in the 1918 and 2009 epidemics. This historical revision was the ground for evaluating the response to treatment including homeopathy in the former epidemics. It is discussed the convenience of including homeopathic prophylaxis grounded on the diagnosis of the epidemic genius among public health actions.

Virus reactivation in a non-cirrhotic HBV patient requiring liver transplantation after cessation of nucleoside analogue therapy

Nucleos(t)ide analogues (NAs) are a mainstay of therapy for chronic hepatitis B (CHB) infections and have a profound effect on hepatitis B virus (HBV) suppression. We report a rare case of HBV reactivation in a CHB patient without cirrhosis following cessation of NA therapy that resulted in acute liver failure requiring liver transplantation. Investigation of the viral genetics and host immune responses suggest that viral mutations known to promote virus replication are associated with reactivation, whereas adaptive immunity to HBV remained defective in this patient. Viral sequencing may be useful for identifying mutations that are unfavorable for therapy withdrawal.

A dentate gyrus-CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation

Memories encoded in the dentate gyrus (DG)-CA3 circuit of the hippocampus are routed from CA1 to anterior cingulate cortex (ACC) for consolidation. Although CA1 parvalbumin inhibitory neurons (PV INs) orchestrate hippocampal-cortical communication, we know less about CA3 PV INs or DG-CA3 principal neuron-IN circuit mechanisms that contribute to evolution of hippocampal-cortical ensembles during memory consolidation. Using viral genetics to selectively enhance dentate granule cell recruitment of CA3 PV INs and feed-forward inhibition (FFI) in CA3 and longitudinal in vivo calcium imaging, we demonstrate that FFI facilitates formation and maintenance of context-associated neuronal ensembles in CA1. Increasing FFI in DG-CA3 promoted context specificity of neuronal ensembles in ACC over time and enhanced long-term contextual fear memory. Our findings illuminate how FFI in DG-CA3 dictates evolution of ensemble properties in CA1 and ACC during memory consolidation and suggest a teacher-like function for hippocampal CA1 in stabilization and re-organization of cortical representations.

Nipah virus dynamics in bats and implications for spillover to humans

Nipah virus (NiV) is an emerging bat-borne zoonotic virus that causes near-annual outbreaks of fatal encephalitis in South Asia—one of the most populous regions on Earth. In Bangladesh, infection occurs when people drink date-palm sap contaminated with bat excreta. Outbreaks are sporadic, and the influence of viral dynamics in bats on their temporal and spatial distribution is poorly understood. We analyzed data on host ecology, molecular epidemiology, serological dynamics, and viral genetics to characterize spatiotemporal patterns of NiV dynamics in its wildlife reservoir,Pteropus mediusbats, in Bangladesh. We found that NiV transmission occurred throughout the country and throughout the year. Model results indicated that local transmission dynamics were modulated by density-dependent transmission, acquired immunity that is lost over time, and recrudescence. Increased transmission followed multiyear periods of declining seroprevalence due to bat-population turnover and individual loss of humoral immunity. Individual bats had smaller host ranges than otherPteropusspecies (spp.), although movement data and the discovery of a Malaysia-clade NiV strain in eastern Bangladesh suggest connectivity with bats east of Bangladesh. These data suggest that discrete multiannual local epizootics in bat populations contribute to the sporadic nature of NiV outbreaks in South Asia. At the same time, the broad spatial and temporal extent of NiV transmission, including the recent outbreak in Kerala, India, highlights the continued risk of spillover to humans wherever they may interact with pteropid bats and the importance of limiting opportunities for spillover throughoutPteropus’s range.

Simultaneous Viral Whole-Genome Sequencing and Differential Expression Profiling in Respiratory Syncytial Virus Infection of Infants

Targeted metagenomics using strand-specific libraries with target enrichment is a sensitive, generalized approach to pathogen sequencing and transcriptome profiling. Using this method, we recovered 13 (76%) complete human respiratory syncytial virus (RSV) genomes from 17 clinical respiratory samples, reconstructed the phylogeny of the infecting viruses, and detected differential gene expression between 2 RSV subgroups, specifically, a lower expression of the P gene and a higher expression of the M2 gene in RSV-A than in RSV-B. This methodology can help to relate viral genetics to clinical phenotype and facilitate ongoing population-level RSV surveillance and vaccine development. Clinical Trials Registration. NCT03627572 and NCT03756766.

Full Genomic Sequencing of Vesicular Stomatitis Virus Isolates from the 2004–2006 US Outbreaks Reveals Associations of Viral Genetics to Environmental Variables

Vesicular stomatitis (VS) outbreaks in the western USA occur cyclically, approximately every 8–10 years. Phylogenetic evidence based on a 450 nt region of the P coding sequences suggests that the initial introduction was a single viral lineage closely related to those circulating in endemic areas of Mexico. In 2004, a VS outbreak was initiated in southern NM and TX, and spread as far north as northern CO. Subsequently, in 2005, VS cases appeared in nine states (AZ, CO, ID, MT, NE, NM, TX, UT and WY), and in 2006, VS reappeared only in WY. Phylogenetic analysis suggested that a single VS virus of New Jersey (VSNJV) lineage caused the 2004 outbreak, and re-emerged in 2005 and 2006. The mechanisms of VS emergence and re-emergence remain unclear. Here, we used near full-length genomic sequences of 60 viral strains isolated from 2004–2006 in the US and Mexico to determine the phylogeographic relationships and environmental variables associated with the outbreak dynamics. The results confirmed that a single VSNJV lineage caused the 2004–2006 US outbreaks, and that its closest ancestor was a virus circulating in Colima, Mexico in 2004. We also present evidence that the virus lineage overwintered in 2005 and 2006. Furthermore, rather than a simple geographic relationship, specific viral sublineages or patristic groups were associated to environmental variables, particularly precipitation and temperature. The results confirm the role of environmental factors in the evolution and spread of VSNJV in the USA.

Evolution and Genetic Diversity of Primate Cytomegaloviruses

Cytomegaloviruses (CMVs) infect many mammals, including humans and non–human primates (NHPs). Human cytomegalovirus (HCMV) is an important opportunistic pathogen among immunocompromised patients and represents the most common infectious cause of birth defects. HCMV possesses a large genome and very high genetic diversity. NHP–infecting CMVs share with HCMV a similar genomic organization and coding content, as well as the course of viral infection. Recent technological advances have allowed the sequencing of several HCMV strains from clinical samples and provided insight into the diversity of NHP–infecting CMVs. The emerging picture indicates that, with the exclusion of core genes (genes that have orthologs in all herpesviruses), CMV genomes are relatively plastic and diverse in terms of gene content, both at the inter– and at the intra–species level. Such variability most likely underlies the strict species–specificity of these viruses, as well as their ability to persist lifelong and with relatively little damage to their hosts. However, core genes, despite their strong conservation, also represented a target of adaptive evolution and subtle changes in their coding sequence contributed to CMV adaptation to different hosts. Indubitably, important knowledge gaps remain, the most relevant of which concerns the role of viral genetics in HCMV–associated human disease.

Genetic Determinants of the Re-Emergence of Arboviral Diseases

Mosquito-borne diseases constitute a large portion of infectious diseases, causing more than 700,000 deaths annually. Mosquito-transmitted viruses, such as yellow fever, dengue, West Nile, chikungunya, and Zika viruses, have re-emerged recently and remain a public health threat worldwide. Global climate change, rapid urbanization, burgeoning international travel, expansion of mosquito populations, vector competence, and host and viral genetics may all together contribute to the re-emergence of arboviruses. In this brief review, we summarize the host and viral genetic determinants that may enhance infectivity in the host, viral fitness in mosquitoes and viral transmission by mosquitoes.