Two Novel Parvoviruses in Frugivorous New and Old World Bats

Bats, a globally distributed group of mammals with high ecological importance, are increasingly recognized as natural reservoir hosts for viral agents of significance to human and animal health. In the present study, we evaluated pools of blood samples obtained from two phylogenetically distant bat families, in particular from flying foxes (Pteropodidae), Eidolon helvum in West Africa, and from two species of New World leaf-nosed fruit bats (Phyllostomidae), Artibeus jamaicensis and Artibeus lituratus in Central America. A sequence-independent virus discovery technique (VIDISCA) was used in combination with high throughput sequencing to detect two novel parvoviruses: a PARV4-like virus named Eh-BtPV-1 in Eidolon helvum from Ghana and the first member of a putative new genus in Artibeus jamaicensis from Panama (Aj-BtPV-1). Those viruses were circulating in the corresponding bat colony at rates of 7–8%. Aj-BtPV-1 was also found in Artibeus lituratus (5.5%). Both viruses were detected in the blood of infected animals at high concentrations: up to 10E8 and to 10E10 copies/ml for Aj-BtPV-1 and Eh-BtPV-1 respectively. Eh-BtPV-1 was additionally detected in all organs collected from bats (brain, lungs, liver, spleen, kidneys and intestine) and spleen and kidneys were identified as the most likely sites where viral replication takes place. Our study shows that bat parvoviruses share common ancestors with known parvoviruses of humans and livestock. We also provide evidence that a variety of Parvovirinae are able to cause active infection in bats and that they are widely distributed in these animals with different geographic origin, ecologies and climatic ranges

1283. Pretreatment HIV-1 Drug Resistance in Transmission Clusters of the Cologne-Bonn Region, Germany

Abstract Background In Germany, previous reports have demonstrated transmitted HIV-1 drug resistance mutations (DRM) in 10% of newly diagnosed individuals, affecting treatment failure and the choice of antiretroviral therapy (ART). Here, we sought to understand the molecular epidemiology of HIV DRM transmission throughout the Cologne-Bonn region, an area with one of the highest rate of new HIV infections in Europe (13.7 per 100,000 habitants). Methods We analyzed 714 HIV-1 ART naïve infected individuals diagnosed at the University Hospitals Cologne and Bonn between 2001 and 2016. Screening for DRM was performed according to the Stanford University Genotypic Resistance Interpretation. Shared DRM were defined as any DRM present in genetically linked individuals (<1.5% genetic distance). Phylogenetic and network analyses were performed to infer putative relationships and shared DRMs. Results We detected 123 DRMs in our study population (17.2% of all sequences). Prevalence of any DRM was comparable among risk groups and was highest among people from an endemic area (i.e., country with HIV prevalence >1%) (11/51, 21.6%). Nucleoside-and non-nucleoside reverse transcriptase inhibitor (NRTI/NNNRTI) resistance mutations were detected in 49 (7%) and 97 (13.6%) individuals, with the E138A in 29 (4.1%) and K103N in 11 (1.5%) being the most frequent. Frequency of DRM was comparable in clustering and not clustering individuals (17.1% vs. 17.5%). Transmission network analysis indicated that the frequency of DRM in clustering individuals was the highest in PWID (3/7, 42.9%) (Figure 1A). Genetically linked individuals harboring shared DRMs were more likely to live in suburban areas than in Central Cologne (18.8% vs. 8% of clustering sequences with DRM; Figure 1B). Conclusion The rate of DRMs was exceptionally high in the Cologne/Bonn area. Network analysis elucidated frequent cases of shared DRMs among genetically linked individuals, revealing the potential spread of DRMs and the need to prevent onward transmission of DRM in the Cologne-Bonn area. Disclosures M. Hoenigl, Gilead, Basilea, Merck: Speaker’s Bureau, Research grant and Speaker honorarium

1280. Geospatial Spread of HIV in the Cologne-Bonn Region, Germany: From 2001 to 2016

Abstract Background Geographical targeting of interventions of hotspots of HIV transmission increases the impact of HIV intervention. We combined molecular epidemiology and geospatial analyses to provide insights into the drivers of HIV transmission and the contribution of geographical hot spots to the rapidly evolving local HIV epidemic of Cologne-Bonn. Methods We included 714 HIV-1-infected ART naïve individuals, followed at the University Hospitals Cologne and Bonn between 2001 and 2016. Phylogenetic and network analyses were performed to infer putative relationships. Assortativity index (AI, i.e., shared attributes) and characteristics of genetically linked individuals were analyzed. The geospatial diffusion of the local epidemic (i.e., viral gene flow) was evaluated using a Slatkin-Maddison approach. Geospatial dispersal of local HIV transmission was determined by calculating the average distance between genetically linked individuals (centroids of 3-digit zip code of residency, ArcGIS®). Results Of 714 sequences, 217 (30.4%) had a putative linkage with at least one other sequence, forming 77 clusters (size range: 2–8). Genetically linked individuals were significantly more likely to live in suburban areas (P = 0.035), <30 years of age (P = 0.013), infected with HIV-1 subtype B (P = 0.002). AI for concurrent area of residency showed that individuals were nonassortative in the network (−0.0026, P = 0.046), indicating that clustering individuals tended to cluster with individuals living in a different zip code. Geospatial analyses revealed that the median distance between genetically linked individuals was 23.4 km, significantly lower than expected (median 39.68 km; P < 0.001) (Figure 1A). Slatkin Maddison analyses revealed increased gene flow originating from Central Cologne toward the surrounding areas (P < 0.001, Figure 1B). Conclusion Phylogeographic analysis suggests that central Cologne may be a significant driver of the regional epidemic. While clustering individuals lived closer than unlinked individuals, they were less likely to be linked to others from their same zip code. This may reflect individuals reaching out of their neighborhoods and social circles to meet new partners. Disclosures All authors: No reported disclosures

Drug Resistance Spread in 6 Metropolitan Regions, Germany, 2001-2018

We analyzed 1,397 HIV-1 pol sequences of antiretroviral therapy-naive patients in a total of 7 university hospitals in Bonn, Cologne, Frankfurt, Hamburg, Hannover, and Munich, Germany. Phylogenetic and network analysis elucidated numerous cases of shared drug resistance mutations among genetically linked patients; K103N was the most frequently shared mutation

Detection of Eh-BtPV-1 in different body compartments of 7 <i>Eidolon helvum</i> bats.^a

a<p>Viral concentrations are indicated as copies/ml in serum and copies/g of tissue obtained from different organs; NEG = negative; NA = not available. The boldface viral concentrations indicate organs with a concentration at least 10 fold higher than serum.</p

Identity ranges (%) of the 3 ORFs both at amino acid (bold) and nucleotide level between species in the PARV4-like viruses^a.

a<p>Eh-BtPV-1 (<i>Eidolon helvum Bat Parvovirus</i> 1), PARV4-g1/3 (<i>Human Parvovirus 4</i> genotypes 1, NC_007018, 2, DQ873391, 3, EU874248), ChimpPTV (<i>Chimpanzee PARV4</i>, HQ113143), PHoV (<i>Porcine Hokovirus</i>, EU200673), BHoV (<i>Bovine Hokovirus</i>, EU200670).</p

Three types of Aj-BtPV-1.

<p>The phylogenetic tree was based on a 740 nt fragment (nucleotides 3820–4561) of Aj-BtPV identified in <i>Artibeus jamaicensis</i> and <i>Artibeus lituratus</i> (#174) bats from Panama, showing the 3 different viral types (panel A). Identity values (in percentage) within and between the 3 types are shown in panel B.</p

Primers used in this study for screening, sequencing and quantifying Eh-BtPV-1 and Aj-BtPV-1.

<p>Primers used in this study for screening, sequencing and quantifying Eh-BtPV-1 and Aj-BtPV-1.</p

Genome organization of Eh-BtPV-1 and of representative members of the PARV4-like genus.

<p>Indicated are the main ORFs (gray, coding frame indicated in parenthesis) and the PLA₂ motif position (purple). On the top the identity within the alignment is shown. Accession numbers: PHoV, EU200673; BHoV, EU200670; ChimpPTV, HQ113143; PARV4, AY622943. Figure was made with Geneious v5.1 software <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029140#pone.0029140-Drummond1" target="_blank">[52]</a>.</p

Epidemiological and clinical insights into the enterovirus D68 upsurge in Europe 2021/22 and the emergence of novel B3-derived lineages, ENPEN multicentre study

International audienceEnterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages