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Natural scrub typhus antibody suppresses HIV CXCR4(X4) viruses

George Watt, Pacharee Kantipong, Thierry Burnouf, Cecilia Shikuma, Sean Philpott
  • George Watt
    Department of Medicine, John A. Burns School of Medicine, University of Hawai’i at Manoa, Honolulu, HI, United States | gwattth@yahoo.com
  • Pacharee Kantipong
    Department of Internal Medicine, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand
  • Thierry Burnouf
    Human Protein Process Sciences, Lille, France and Taipei Medical University, Taipei, Taiwan, Province of China
  • Cecilia Shikuma
    Department of Medicine, John A. Burns School of Medicine, University of Hawai’i at Manoa, Honolulu, HI, United States
  • Sean Philpott
    The Bioethics Program, Union Graduate College, Schenectady, NY, United States

Abstract

Viral load generally rises in HIV-infected individuals with a concomitant infection, but falls markedly in some individuals with scrub typhus (ST), a common Asian rickettsial infection. ST infection appears to shift the viral population from CXCR4-using (X4) to CCR5-utilizing (R5) strains, and there is evidence of cross-reactivity between ST-specific antibodies and HIV-1. We examined the mechanism of ST suppression of HIV by measuring the effects of ST infection on X4 and R5 viruses in vivo and in vitro, and assessing the relative contributions of antibodies and chemokines to the inhibitory effect. In vivo, a single scrub typhus plasma infusion markedly reduced the subpopulation of HIV-1 viruses using the X4 co-receptor in all 8 recipients, and eliminated X4 viruses 6 patients. In vitro, the 14 ST sera tested all inhibited the replication of an X4 but not an R5 virus. This inhibitory effect was maintained if ST sera were depleted of chemokines but was lost upon removal of antibodies. Sera from ST-infected mice recognized a target that co-localized with X4 HIV gp120 in immunofluorescent experiments. These in vivo and in vitro data suggest that acute ST infection generates cross-reactive antibodies that produce potent suppression of CXCR4- but not CCR5-using HIV-1 viruses. ST suppression of HIV replication could reveal novel mechanisms that could be exploited for vaccination strategies, as well as aid in the development of fusion inhibitors and other new therapeutic regimens. This also appears to be the first instance where one pathogen is neutralized by antibody produced in response to infection by a completely unrelated organism.

Keywords

HIV-1, scrub typhus, antibody, Orientia tsutsugamushi, AIDS

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Submitted: 2012-12-22 16:01:17
Published: 2013-05-15 17:17:07
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Copyright (c) 2013 George Watt, Pacharee Kantipong, Thierry Burnouf, Cecilia Shikuma, Sean Philpott

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