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 STinfected 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.

Original languageEnglish
Pages (from-to)e8
JournalInfectious Disease Reports
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 22 2013

Fingerprint

Scrub Typhus
HIV Antibodies
Viruses
Antibodies
HIV-1
Infection
HIV
Chemokines
Serum
HIV Envelope Protein gp120
Cross Infection
Viral Load
Vaccination

Keywords

  • Journal Article
  • Review

Cite this

Natural Scrub Typhus Antibody Suppresses HIV CXCR4(X4) Viruses. / Watt, George; Kantipong, Pacharee; Burnouf, Thierry Pierre Robert; Shikuma, Cecilia; Philpott, Sean.

In: Infectious Disease Reports, Vol. 5, No. 1, 22.01.2013, p. e8.

Research output: Contribution to journalArticle

Watt, George ; Kantipong, Pacharee ; Burnouf, Thierry Pierre Robert ; Shikuma, Cecilia ; Philpott, Sean. / Natural Scrub Typhus Antibody Suppresses HIV CXCR4(X4) Viruses. In: Infectious Disease Reports. 2013 ; Vol. 5, No. 1. pp. e8.
@article{c04d1a7bbc02477caf5b62e1080d4247,
title = "Natural Scrub Typhus Antibody Suppresses HIV CXCR4(X4) Viruses",
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 STinfected 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 = "Journal Article, Review",
author = "George Watt and Pacharee Kantipong and Burnouf, {Thierry Pierre Robert} and Cecilia Shikuma and Sean Philpott",
year = "2013",
month = "1",
day = "22",
doi = "10.4081/idr.2013.e8",
language = "English",
volume = "5",
pages = "e8",
journal = "Infectious Disease Reports",
issn = "2036-7430",
publisher = "PagePress",
number = "1",

}

TY - JOUR

T1 - Natural Scrub Typhus Antibody Suppresses HIV CXCR4(X4) Viruses

AU - Watt, George

AU - Kantipong, Pacharee

AU - Burnouf, Thierry Pierre Robert

AU - Shikuma, Cecilia

AU - Philpott, Sean

PY - 2013/1/22

Y1 - 2013/1/22

N2 - 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 STinfected 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.

AB - 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 STinfected 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.

KW - Journal Article

KW - Review

U2 - 10.4081/idr.2013.e8

DO - 10.4081/idr.2013.e8

M3 - Article

VL - 5

SP - e8

JO - Infectious Disease Reports

JF - Infectious Disease Reports

SN - 2036-7430

IS - 1

ER -