Biology subjects

Telford, S.

Publications and source records attributed to Telford, S..

4 recordsLinked to original sources

bioRxiv2026

Deer tick virus genotypes are perpetuated by different modes of transmission

Deer tick virus (DTV), or lineage II Powassan virus, is an emergent tick-borne encephalitis virus in North America. Survivors frequently sustain neurologic sequelae. Nationally reported cases have been increasing. DTV is thought to be maintained in nature by multiple modes including horizontal transmission (from viremic host to tick), cofeeding transmission (between ticks feeding nearby) and by transovarial transmission (female to progeny). Analysis of the relative importance of each mode has been hindered by low enzootic transmission. In 2021, Marthas Vineyard, Massachusetts experienced an epizootic that allowed us to probe the modes of transmission on the island. We detected virus in 7.8% of questing deer tick nymphs (161 of 2063) and in 0.3% of lone star nymphs (2 of 678). Infected ticks had a highly focal distribution; 56% of infected ticks derived from only 4 of 71 collection sites. Tick mitochondrial genome sequencing demonstrated that infected ticks were not more likely to be siblings than negative ticks and, therefore, were unlikely to have inherited the infection. Whole viral genome sequencing revealed the presence of 3 genotypes, 58% were type1, 0.6% type2, and 13.7% type3. Tick host bloodmeal identification analyses determined that nymphs infected with type1 were significantly associated with having fed on shrews (50 of 94 type1 ticks, odds ratio=2.3, p<0.001). This is consistent with shrews serving as a reservoir. Ticks infected with type3, however, had no host associations, consistent with infection acquired by cofeeding. It may be that local DTV genetic variation is shaped by transmission modes or host associations. ImportanceDeer tick virus (DTV; Powassan lineage II) is a tick-borne encephalitis virus that causes a rare zoonosis in North America. Cases have been increasingly reported within the last decade. Is the recent risk trend due to increased transmission? How this virus is perpetuated in nature is not well understood. We took advantage of a natural epizootic on Marthas Vineyard to probe how the ticks there had become infected. Using a combination of viral whole genome sequencing and bloodmeal remnant identification in ticks, we find that the mode of transmission varied by viral genotype. One genotype is associated with ticks that had fed on shrews, and another did not depend on a specific reservoir host. Host associations may drive genetic diversity of deer tick virus and thus local host population dynamics may influence zoonotic risk.

ecology↗

bioRxiv2024

Heritable Immunization Establishes a New Model for Pathogen Control

Heritable immunization represents a promising approach for controlling infectious diseases by embedding immunity directly into the genomes of wild species that spread human pathogens. Here, we report the genetic engineering of Mus musculus to produce a neutralizing, protective single-chain antibody against Borrelia burgdorferi, the causative agent of Lyme disease. Engineered mice stably produced a LA-2 scFv-albumin fusion protein across multiple generations, demonstrating robust heritability and stability of gene expression. Following sequential challenges with infected and uninfected ticks, heterozygous mice exhibited strong resistance to infection, effectively interrupting the Borrelia burgdorferi disease transmission cycle. Having recently established novel protocols to genetically engineer the white-footed mouse, Peromyscus leucopus, a key reservoir of Lyme disease, these findings demonstrate the feasibility of heritable immunization as a potential strategy for mitigating Lyme disease transmission in the environment. More broadly, engineered reservoir immunity may offer a generalizable approach to controlling vector-borne and zoonotic disease with profound potential to improve human health.

bioengineering↗

bioRxiv2023

Comparative reservoir competence of Peromyscus leucopus and mouse models for Borrelia burgdorferi B31

Borrelia burgdorferi, a Lyme disease spirochete, causes a range of acute and chronic maladies in humans. However, a primary vertebrate reservoir in the United States, the white-footed deermouse Peromyscus leucopus, is reported not to have reduced fitness following infection. While laboratory strains of Mus musculus mice have successfully been leveraged to model acute human Lyme disease, the ability for these rodents to model B. burgdorferi-P. leucopus interactions remains understudied. Here we compared infection of P. leucopus with B. burgdorferi B31 with infection of the traditional B. burgdorferi murine models--C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that B. burgdorferi were able to reach much higher burdens (10- to 30-times higher) in multiple M. musculus skin sites, and that the overall dynamics of infection differed between the two rodent species. We also found that P. leucopus remained transmissive to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi in the skin, which we hypothesize leads to reduced bacterial viability and rodent-to-tick transmission in these hosts. Similarly, we also observe evidence of inflammation in infected P. leucopus hearts. These observations provide new insight into reservoir species and the B. burgdorferi enzootic cycle. ImportanceA Lyme disease-causing bacteria, Borrelia burgdorferi, must alternate between infecting a vertebrate host--usually rodents or birds--and ticks. In order to be successful in that endeavor the bacteria must avoid being killed by the vertebrate host before it can infect a new larval tick. In this work we examine how B. burgdorferi and one of its primary vertebrate reservoirs, Peromyscus leucopus, interact during an experimental infection. We find that B. burgdorferi appear to colonize its natural host less successfully than conventional laboratory mouse models which aligns with a sustained seemingly anti-bacterial response by P. leucopus against the microbe. These data enhance our understanding of P. leucopus host-pathogen interactions and could potentially serve as a foundation to uncover ways to disrupt the spread of B. burgdorferi in nature.

microbiology↗

bioRxiv2017

Zoonotic Babesia microti in the northeastern U.S.: evidence for the expansion of a specific parasite lineage

The recent range expansion of human babesiosis in the northeastern United States, once found only in restricted coastal sites, is not well understood. This study sought to utilize a large number of samples to examine the population structure of the parasites on a fine scale to provide insights into the mode of emergence across the region. 228 B. microti samples collected in endemic northeastern U.S. sites were genotyped using published VNTR markers. The genetic diversity and population structure were analysed on a geographic scale using Phyloviz and TESS. Three distinct populations were detected in northeastern US, each dominated by a single ancestral type. In contrast to the limited range of the Nantucket and Cape Cod populations, the mainland population dominated from New Jersey eastward to Boston. Ancestral populations of B. microti were sufficiently isolated to differentiate into distinct populations. Despite this, a single population was detected across a large geographic area of the northeast that historically had at least 3 distinct foci of transmission, central New Jersey, Long Island and southeastern Connecticut. We conclude that a single B. microti genotype has expanded across the northeastern U.S. The biological attributes associated with this parasite genotype that have contributed to such a selective sweep remain to be identified.\n\nAuthor summaryBabesiosis is a disease caused by a protozoan parasite, Babesia microti, related to malaria. The disease is acquired by the bite of the deer tick, the same tick that transmits Lyme disease. Although Lyme disease rapidly emerged over a wide range within the last 40 years, babesiosis remained rare with an extremely focal distribution. Within the last decade, the number of reports of babesiosis cases has increased from an expanded area of risk, particularly across the mainland of southern New England. We determined whether the expanded risk may be due to local intensification of transmission as opposed to introduction of the parasite. Historical fragmentation of the landscape suggests that sites of B. microti transmission should have been isolated and thus evidence of multiple genetically distinct populations should be found. By a genetic fingerprinting method, we found that samples from the new mainland sites were all genetically similar. We conclude that one parasite genetic lineage has recently expanded its distribution and now dominates, suggesting that it has some phenotypic attribute that may confer a selective advantage over others.

epidemiology↗