Biology subjects

Ries, H. J.

Publications and source records attributed to Ries, H. J..

3 recordsLinked to original sources

bioRxiv2026

Spondweni virus infection in pregnant rhesus macaques causes placental pathology without apparent fetal harm

The 2015-2016 Zika virus (ZIKV) epidemic revealed the potential of flaviviruses to emerge rapidly, cause severe disease, and affect pregnancy outcomes. In 2016, Spondweni virus (SPOV), the closest known relative of ZIKV, was detected in mosquitoes in Haiti, suggesting it may also have the potential to emerge in the Western Hemisphere. The risks that close relatives of ZIKV pose to pregnant individuals are not well understood. Previously, we showed that SPOV can cause fetal demise, placental pathology, and vertical transmission in a mouse model. Here we report SPOVs pathogenic potential in pregnant rhesus macaques. We inoculated four macaques with SPOV at gestational day 30 (early first trimester) and compared their viral loads and fetal outcomes with those of macaques infected in the first trimester with either African-lineage ZIKV (ZIKV-DAK) or an Asian-lineage ZIKV isolate from Puerto Rico (ZIKV-PR) in previous studies. Plasma viremia persisted 10-31 days in SPOV-inoculated dams, whereas viremia resolved within 10-17 days for ZIKV-DAK and 5-52 days for ZIKV-PR. Cesarean deliveries near term (gestational day 152-157) revealed no demise, premature birth, or gross abnormalities in fetuses of dams inoculated with SPOV or ZIKV-PR. In contrast, under near-identical conditions, all ZIKV-DAK-inoculated dams experienced fetal demise between 12 and 20 days post-inoculation. At cesarean section, we did not detect SPOV RNA above the limit of detection in maternal (e.g., spleen, liver), placental, or fetal tissues, in contrast to previous findings with ZIKV-PR. Histological analysis revealed mononuclear/lymphohistiocytic villitis in all placentas of SPOV-exposed macaques, along with other pathological changes in individual placentas. Our findings suggest that SPOV infection of macaques in early pregnancy may result in placental pathology without overt fetal harm. Our results suggest that flaviviruses in the Spondweni serocomplex, which includes ZIKV and SPOV, may vary in their pathogenic potential during pregnancy. Author SummaryZika virus (ZIKV) can cause fetal harm. Does this risk extend to its closest known relative, Spondweni virus (SPOV)? Should SPOV circulate in humans, what risks would it pose in pregnancy? SPOV can injure fetuses in immunocompromised mice, but the physiology of pregnancy in mice differs greatly from that of humans. We therefore infected pregnant rhesus macaques with SPOV during early gestation and compared maternal viremia, placental pathology, and fetal outcomes with macaques infected with African- or Asian-lineage ZIKVs at the same gestational age. All fetuses survived to near-term pregnancy, fetal tissues were negative for SPOV RNA, and fetal growth tracked within expected ranges. Nonetheless, all SPOV-exposed pregnancies showed placental injury, including mononuclear/lymphohistiocytic villitis and maternal vascular malperfusion. Despite the absence of detectable SPOV RNA in fetal tissues, SPOV RNA persisted at term in maternal-fetal interface tissues in two of four animals. These data indicate placental injury without detectable vertical transmission in this translational model. Our results suggest that SPOV and ZIKV display a wide range of risks to the developing fetus. Identifying viral and host factors that increase the potential for fetal harm will be important for assessing risks posed by emerging viruses in this family.

microbiology↗

bioRxiv2025

Weak selection and stochastic processes limit the emergence of antigenic variants during household transmission of influenza A viruses

Influenza viruses undergo antigenic drift, the gradual accumulation of mutations that cause antigenic changes in the viral surface proteins hemagglutinin (HA) and neuraminidase (NA). Although selection for antigenic variants is detectable on the global scale, the processes by which antigenic variants are generated and selected in individual hosts remain unclear. It has been hypothesized that selection for antigenic variants may occur during the establishment of a new infection, rather than over time in a single host. Here, we leveraged a large household cohort study to assess whether selection was detectable between acutely infected hosts. We investigated influenza A virus evolution using specimens from 384 children and household contacts with RT-PCR-confirmed influenza A infection, representing infections with A(H1N1)pdm09 and A(H3N2) viruses from 2017-19. In agreement with prior studies, we found that acute infections involved weak purifying selection across the viral genome. In addition, we identified 40 transmission events occurring in 31 households. During transmission, evolution between hosts was characterized by tight transmission bottlenecks and weak purifying selection. We found variability in the strength and direction of selection on antigenic regions of HA, but no clear evidence for selection of antigenic variants during transmission. Together, our results indicate that stochastic processes and weak natural selection dominate most acute influenza A virus infections and transmission events, and that selection of antigenic variants during transmission between acutely infected hosts is likely to be exceedingly rare. Author SummaryInfluenza viruses clearly evolve under selective pressure from immune responses in human populations, but recent work suggests that within individual infections random effects are stronger than selection. New viral variants that spread globally must nonetheless emerge in one person and be transmitted onwards--how does this happen? We characterized viral genomes collected over two influenza seasons from 384 children and their household contacts. We detected 40 transmissions among 31 of the households, allowing us to examine how selection acts during infection and transmission. We found that influenza virus genetic diversity is low in infected individuals, and mutations arising in one person are rarely transmitted to their household contacts, consistent with prior reports that influenza virus evolution is tightly constrained within hosts. We further examined all transmission events for evidence of selection between hosts, finding only one mutation that could plausibly affect antibody recognition. However, we found no evidence that this mutation was favored by natural selection. Our results suggest that chance events, together with weak selection, are the main forces affecting influenza virus evolution within and between hosts during typical acute infections. Selection for new variants may be more likely to occur over longer transmission chains and/or during prolonged infections.

evolutionary biology↗

bioRxiv2023

Wolbachia-mediated resistance to Zika virus infection in Aedes aegypti is dominated by diverse transcriptional regulation and weak evolutionary pressures

A promising candidate for arbovirus control and prevention relies on replacing arbovirus-susceptible Aedes aegypti populations with mosquitoes that have been colonized by the intracellular bacterium Wolbachia and thus have a reduced capacity to transmit arboviruses. This reduced capacity to transmit arboviruses is mediated through a phenomenon referred to as pathogen blocking. Pathogen blocking has primarily been proposed as a tool to control dengue virus (DENV) transmission, however it works against a range of viruses, including Zika virus (ZIKV). Despite years of research, the molecular mechanisms underlying pathogen blocking still need to be better understood. Here, we used RNA-seq to characterize mosquito gene transcription dynamics in Ae. aegypti infected with the wMel strain of Wolbachia that are being released by the World Mosquito Program in Medellin, Colombia. Comparative analyses using ZIKV-infected, uninfected tissues, and mosquitoes without Wolbachia revealed that the influence of wMel on mosquito gene transcription is multifactorial. Importantly, because Wolbachia limits, but does not completely prevent, replication of ZIKV and other viruses in coinfected mosquitoes, there is a possibility that these viruses could evolve resistance to pathogen blocking. Therefore, to understand the influence of Wolbachia on within-host ZIKV evolution, we characterized the genetic diversity of molecularly barcoded ZIKV virus populations replicating in Wolbachia-infected mosquitoes and found that within-host ZIKV evolution was subject to weak purifying selection and, unexpectedly, loose anatomical bottlenecks in the presence and absence of Wolbachia. Together, these findings suggest that there is no clear transcriptional profile associated with Wolbachia-mediated ZIKV restriction, and that there is no evidence for ZIKV escape from this restriction in our system. Author SummaryWhen Wolbachia bacteria infect Aedes aegypti mosquitoes, they dramatically reduce the mosquitoes susceptibility to infection with a range of arthropod-borne viruses, including Zika virus (ZIKV). Although this pathogen-blocking effect has been widely recognized, its mechanisms remain unclear. Furthermore, because Wolbachia limits, but does not completely prevent, replication of ZIKV and other viruses in coinfected mosquitoes, there is a possibility that these viruses could evolve resistance to Wolbachia-mediated blocking. Here, we use host transcriptomics and viral genome sequencing to examine the mechanisms of ZIKV pathogen blocking by Wolbachia and viral evolutionary dynamics in Ae. aegypti mosquitoes. We find complex transcriptome patterns that do not suggest a single clear mechanism for pathogen blocking. We also find no evidence that Wolbachia exerts detectable selective pressures on ZIKV in coinfected mosquitoes. Together our data suggest that it may be difficult for ZIKV to evolve Wolbachia resistance, perhaps due to the complexity of the pathogen blockade mechanism.

molecular biology↗