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Home / Equine Research Bank / Infect Immun / Rapid sequential changeover of expressed p44 genes during th...
Infection and immunity2004; 72(12); 6852-6859; doi: 10.1128/IAI.72.12.6852-6859.2004

Rapid sequential changeover of expressed p44 genes during the acute phase of Anaplasma phagocytophilum infection in horses.

Abstract: Anaplasma phagocytophilum immunodominant polymorphic major surface protein P44s have been hypothesized to go through antigenic variation, but the within-host dynamics of p44 expression has not been demonstrated. In the present study we investigated the composition and changes of p44 transcripts in the blood during the acute phase of well-defined laboratory A. phagocytophilum infections in naive equine hosts. Three traveling waves of sequential population changeovers of the p44 transcript species were observed within a single peak of rickettsemia of less than 1 month. During the logarithmic increase, the rapid switch-off of the initial dominant transcript p44-18 occurred regardless of whether the bacterium was transmitted by ticks or by intravenous inoculation. Each of the subsequently dominant p44 transcript species was phylogenetically dissimilar from p44-18. Development of antibody to the hypervariable region of P44-18 during the rickettsemia suggests the suppression of dominance of immuno-cross-reactive p44 populations. When A. phagocytophilum was preincubated with plasma from the infected horse and then coincubated with HL-60 cells, the dominance of the p44-18 transcript was rapidly suppressed in vitro and most of the newly emerged p44 transcript species were previously undetected in this horse. This work provides experimental evidence of within-host p44 antigenic variation. Results suggest that the rapid and synchronized switch of expression is an intrinsic property of p44s reinitiated after transmission to naive mammalian hosts and shaped upon exposure to immune plasma.
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Publication Date: 2004-11-24 PubMed ID: 15557606PubMed Central: PMC529143DOI: 10.1128/IAI.72.12.6852-6859.2004Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates how Anaplasma phagocytophilum, a tick-borne bacterium that infects horses, rapidly changes its expressed p44 surface proteins during the acute phase of infection. This overviews the course of the bacterial infection and the dynamic variation of p44 proteins, demonstrating that this bacteria may utilize strategies to evade the host’s immune response.

Objective of the Research

  • The objective of this research was to investigate the dynamics of p44 protein expression of Anaplasma phagocytophilum during the acute phase of infection in horses. The researchers hypothesized that this bacterium rapidly changes its p44 expression in order to possibly evade the immune response of its host.

Methods and Findings

  • The researchers investigated and observed the changes in p44 transcripts in the blood during laboratory-induced A. phagocytophilum infection in horses, which had not previously been exposed to the bacterium.
  • Three successive waves of population changeovers of different p44 transcript species were observed within a month during the peak infection, indicating rapid turnover and alteration of p44 protein expression by the bacterium.
  • They found that, regardless of how the bacterium was transmitted – either via ticks or through intravenous inoculation – the initial dominant transcript p44-18 was rapidly switched off during the logarithmic increase in bacteria, which is a period of rapid bacterial growth.
  • Subsequent dominant p44 transcripts were drastically different from p44-18 phylogenetically (in evolutionary development), suggesting continuous, rapid antigenic variation.
  • They also noted the development of antibodies against P44-18 during the infection, which may indicate the suppression of immuno-cross-reactive p44 populations.
  • In vitro experiments were carried out where the bacterium was incubated with plasma from an infected horse, along with HL-60 cells. Here, the dominance of p44-18 transcript was quickly suppressed and a majority of the new p44 transcripts were previously undetected in the horse.

Conclusions

  • This research provides experimental evidence that A. phagocytophilum undergoes rapid within-host antigenic variation of its p44 proteins.
  • The results of the study suggest this rapid, synchronized switch of p44 expression may be an intrinsic adaptive response of the bacterium initiated after infection in naive mammalian hosts, and is further shaped upon exposure to immune plasma.
  • This implies that the bacterium may utilize antigenic variation as a potential strategy to evade host immunity and sustain infection.

Cite This Article

APA
Wang X, Rikihisa Y, Lai TH, Kumagai Y, Zhi N, Reed SM. (2004). Rapid sequential changeover of expressed p44 genes during the acute phase of Anaplasma phagocytophilum infection in horses. Infect Immun, 72(12), 6852-6859. https://doi.org/10.1128/IAI.72.12.6852-6859.2004

Publication

Infection and immunity
ISSN: 0019-9567
NlmUniqueID: 0246127
Country: United States
Language: English
Volume: 72
Issue: 12
Pages: 6852-6859

Researcher Affiliations

Wang, Xueqi
  • Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, Columbus, OH 43210-1093, USA.
Rikihisa, Yasuko
    Lai, Tzung-Hui
      Kumagai, Yumi
        Zhi, Ning
          Reed, Stephen M

            MeSH Terms

            • Acute Disease
            • Anaplasma phagocytophilum / genetics
            • Anaplasma phagocytophilum / immunology
            • Animals
            • Antibodies, Bacterial / blood
            • Antigens, Bacterial / genetics
            • Base Sequence
            • Ehrlichiosis / immunology
            • Ehrlichiosis / metabolism
            • Ehrlichiosis / veterinary
            • Horse Diseases / immunology
            • Horses
            • Molecular Sequence Data
            • RNA, Messenger / analysis
            • Reverse Transcriptase Polymerase Chain Reaction

            Grant Funding

            • R01 AI047407 / NIAID NIH HHS
            • R01 AI 47407 / NIAID NIH HHS

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            This article has been cited 24 times.
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