Biology subjects

Peace, A.

Publications and source records attributed to Peace, A..

3 recordsLinked to original sources

bioRxiv2020

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV. Significance statementZika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.

immunology↗

bioRxiv2019

Local control of resource allocation is sufficient to model optimal dynamics in syntrophic systems

Syntrophic systems are common in nature and include forms of obligate mutualisms in which each participating organism or component of an organism obtains from the other an essential nutrient or metabolic product that it cannot provide for itself. Models of how these complementary resources are allocated between partners often assume optimal behavior, but whether mechanisms enabling global control exist in syntrophic systems, and what form they might take, is unknown. Recognizing that growth of plant organs that supply complementary resources, like roots and shoots, can occur autonomously, we present a theory of plant growth in which root-shoot allocation is determined by purely local rules. Each organ uses as much as it can of its locally produced or acquired resource (inorganic nitrogen or photosynthate) and shares only the surplus. Subject to stoichiometric conditions that likely hold for most plants, purely local rules produce the same optimal allocation as would global control, even in a fluctuating environment, with sharing the surplus being the specific mechanism stabilizing syntrophic dynamics. Our local control model contributes a novel approach to plant growth modeling because it assumes a simple mechanism of root:shoot allocation that can be considered a higher-level physiological rule, from which the optimal growth outcome emerges from the systems dynamics, rather than being built into the model. Moreover, our model is general, in that the mechanism of sharing the surplus can readily be adapted to many obligate syntrophic relationships.

plant biology↗

bioRxiv2019

Evidence of adaptive host and vector manipulation by plant viruses revealed through combined meta-analysis and modeling approaches.

A growing number of studies indicate that plant viruses enhance their own transmission by modifying host phenotypes and vector behavior, leading to the hypothesis that such effects are manipulations resulting from virus adaptations. However, few studies have linked putative manipulations with virus components, and the true frequency and magnitude of host and vector manipulation across virus taxa remains unknown. To address this knowledge gap, we performed a meta-analysis to quantify convergence in virus effects on hosts and vectors across taxonomic groups that share transmission mechanism traits, and thereby stand to benefit from similar sequences of vector behavior. We then combined meta-analysis outputs with an epidemiological model to assess consequences of manipulation for virus spread. Overall, transmission mechanism traits strongly predicted the magnitude and nature of virus effects on vector preferences and performance. Models parameterized with meta-analysis data demonstrate that manipulation effects enhance virus spread, and that viruses with long acquisition times and retention durations are under strong selection pressure to manipulate transmission. By combining meta-analysis with epidemiological modeling, our results confirm that host and vector manipulation are important aspects of plant virus ecology and evolution while emphasizing the need to incorporate more pathosystems and transmission mechanism traits in future studies.

ecology↗