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Real-time monitoring of disease progression in rhesus macaques infected with Borrelia turicatae by tick bite.

ABSTRACT: The hallmark of disease caused by tick- and louse-borne relapsing fever due to Borrelia infection is cyclic febrile episodes, which in humans results in severe malaise and may lead to death. To evaluate the pathogenesis of relapsing fever due to spirochetes in an animal model closely related to humans, disease caused by Borrelia turicatae after tick bite was compared in 2 rhesus macaques in which radiotelemetry devices that recorded body temperatures in 24-hour increments were implanted. The radiotelemetry devices enabled real-time acquisition of core body temperatures and changes in heart rates and electrocardiogram intervals for 28 consecutive days without the need to constantly manipulate the animals. Blood specimens were also collected from all animals for 14 days after tick bite, and spirochete densities were assessed by quantitative polymerase chain reaction. The complexity of disease caused by relapsing-fever spirochetes was demonstrated in the nonhuman primates monitored in real time. The animals experienced prolonged episodes of hyperthermia and hypothermia; disruptions in their diurnal patterns and repolarization of the heart were also observed. This is the first report of the characterizing disease progression with continuous monitoring in an animal model of relapsing fever due to Borrelia infection.

SUBMITTER: Lopez JE

PROVIDER: S-EPMC4326309 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Real-time monitoring of disease progression in rhesus macaques infected with Borrelia turicatae by tick bite.

Lopez Job E JE Vinet-Oliphant Heather H Wilder Hannah K HK Brooks Christopher P CP Grasperge Britton J BJ Morgan Timothy W TW Stuckey Kerstan J KJ Embers Monica E ME

The Journal of infectious diseases 20140530 10

The hallmark of disease caused by tick- and louse-borne relapsing fever due to Borrelia infection is cyclic febrile episodes, which in humans results in severe malaise and may lead to death. To evaluate the pathogenesis of relapsing fever due to spirochetes in an animal model closely related to humans, disease caused by Borrelia turicatae after tick bite was compared in 2 rhesus macaques in which radiotelemetry devices that recorded body temperatures in 24-hour increments were implanted. The rad ...[more]

PMID: 24879799

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Project description:Vector competence refers to the ability of an arthropod to acquire, maintain, and successfully transmit a microbial pathogen. Tick-borne relapsing fever (TBRF) spirochetes are globally distributed pathogens, and most species are transmitted by argasid ticks of the genus Ornithodoros. A defining characteristic in vector competence is an apparent specificity of a species of TBRF spirochete to a given tick species. In arid regions of the southern United States, Borrelia turicatae is the primary cause of TBRF. Interestingly, there are two populations of the tick vector distributed throughout this region. Ornithodoros turicata is a western population that ranges from California to Texas. There is a gap through Louisiana, Mississippi, and Alabama where the tick has not been identified. An isolated eastern population exists in Florida and was designated a subspecies, O. turicata americanus. A knowledge gap that exists is the poor understanding of vector competence between western and eastern populations of ticks for B. turicatae. In this study, we generated uninfected colonies of O. turicata that originated in Texas and Kansas and of O. turicataamericanus. B. turicatae acquisition, maintenance through the molt, and subsequent transmission were evaluated. Our findings revealed significant differences in murine infection after feeding infected O. turicata and O. turicataamericanus ticks on the animals. Interestingly, the salivary glands of both tick populations were colonized with B. turicatae to similar densities. Our results suggest that the salivary glands of the tick colonies assessed in this study impact vector competence of the evaluated B. turicatae isolates.IMPORTANCE Several knowledge gaps exist in the vector competence of various geographical populations of O. turicata that transmit B. turicatae A western population of this tick is distributed from California to Texas, and an eastern population exists in Florida. Utilizing western and eastern populations of the vector, we studied acquisition and transmission of two B. turicatae isolates. Regardless of the isolate used, infection frequencies were poor in mice after the eastern population feeding on them. Since salivary gland colonization is essential for B. turicatae transmission, these tissues were further evaluated. Interestingly, the salivary glands from the two populations were similarly colonized with B. turicatae. These findings suggest the role of tick saliva in the establishment of infection and that the salivary glands may be a bottleneck for successful transmission.

Project description:UnlabelledTripartite motif-containing protein 5α (TRIM5α) is considered to be a potential target for cell-based gene modification therapy against human immunodeficiency virus type 1 (HIV-1) infection. In the present study, we used a relevant rhesus macaque model of infection with simian immunodeficiency virus from sooty mangabey (SIVsm) to evaluate the effect of TRIM5α restriction on clinical outcome. For macaques expressing a restrictive TRIM5 genotype, the disease outcomes of those infected with the wild-type TRIM-sensitive SIVsm strain and those infected with a virus with escape mutations in the capsid were compared. We found that TRIM5α restriction significantly delayed disease progression and improved the survival rate of SIV-infected macaques, supporting the feasibility of exploiting TRIM5α as a target for gene therapy against HIV-1. Furthermore, we also found that preservation of memory CD4 T cells was associated with protection by TRIM5α restriction, suggesting memory CD4 T cells or their progenitor cells as an ideal target for gene modification. Despite the significant effect of TRIM5α restriction on survival, SIV escape from TRIM5α restriction was also observed; therefore, this may not be an effective stand-alone strategy and may require combination with other targets.ImportanceRecent studies suggest that it may be feasible not only to suppress viral replication with antiviral drugs but also potentially to eliminate or "cure" human immunodeficiency virus (HIV) infection. One approach being explored is the use of gene therapy to introduce genes that can restrict HIV replication, including a restrictive version of the host factor TRIM5α. TRIM5 was identified as a factor that restricts HIV replication in macaque cells. The rhesus gene is polymorphic, and some alleles are restrictive for primary SIVsm isolates, although escape mutations arise late in infection. Introduction of these escape mutations into the parental virus conferred resistance to TRIM5 on macaques. The present study evaluated these animals for long-term outcomes and found that TRIM5α restriction significantly delayed disease progression and improved the survival rate of SIV-infected macaques, suggesting that this could be a valid gene therapy approach that could be adapted for HIV.

Dataset Information

Real-time monitoring of disease progression in rhesus macaques infected with Borrelia turicatae by tick bite.

Publications

Real-time monitoring of disease progression in rhesus macaques infected with Borrelia turicatae by tick bite.

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