Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo

Atfa Sassi; Beda Brichacek; Sara Hieny; Felix Yarovinsky; Hana Golding; Jean Charles Grivel; Alan Sher; Leonid Margolis

doi:10.1016/j.micinf.2009.08.004

Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo

Atfa Sassi, Beda Brichacek, Sara Hieny, Felix Yarovinsky, Hana Golding, Jean Charles Grivel, Alan Sher, Leonid Margolis

Immunology

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii-encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants.

Original language	English (US)
Pages (from-to)	1106-1113
Number of pages	8
Journal	Microbes and Infection
Volume	11
Issue number	14-15
DOIs	https://doi.org/10.1016/j.micinf.2009.08.004
State	Published - Dec 2009

Keywords

Cyclophilin
Ex vivo
HIV
Human lymphoid tissue
Toxoplasma gondii

ASJC Scopus subject areas

Microbiology
Immunology
Infectious Diseases

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10.1016/j.micinf.2009.08.004

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title = "Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo",

abstract = "Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii-encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants.",

keywords = "Cyclophilin, Ex vivo, HIV, Human lymphoid tissue, Toxoplasma gondii",

author = "Atfa Sassi and Beda Brichacek and Sara Hieny and Felix Yarovinsky and Hana Golding and Grivel, {Jean Charles} and Alan Sher and Leonid Margolis",

note = "Funding Information: We thank Dr. M. Santi and the entire staff of the Department of Pathology of Children's National Medical Center for their generous assistance in obtaining human tonsillar tissues. We also thank Dr. D. Kabat of the Department of Biochemistry and Molecular Biology and Proteomics Shared Resource, Oregon Health and Science University, Portland, OR, for providing JR-CSF. This research was supported, in part, by the Intramural Research Program of the NIH, National Institute of Child Health, the National Institute of Allergy and Infectious Diseases and Human Development and by the Intramural AIDS Targeted Anti-viral Program (IATAP) of the NIH.",

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AU - Sassi, Atfa

AU - Brichacek, Beda

AU - Hieny, Sara

AU - Yarovinsky, Felix

AU - Golding, Hana

AU - Grivel, Jean Charles

AU - Sher, Alan

AU - Margolis, Leonid

N1 - Funding Information: We thank Dr. M. Santi and the entire staff of the Department of Pathology of Children's National Medical Center for their generous assistance in obtaining human tonsillar tissues. We also thank Dr. D. Kabat of the Department of Biochemistry and Molecular Biology and Proteomics Shared Resource, Oregon Health and Science University, Portland, OR, for providing JR-CSF. This research was supported, in part, by the Intramural Research Program of the NIH, National Institute of Child Health, the National Institute of Allergy and Infectious Diseases and Human Development and by the Intramural AIDS Targeted Anti-viral Program (IATAP) of the NIH.

PY - 2009/12

Y1 - 2009/12

N2 - Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii-encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants.

AB - Critical events of HIV-1 pathogenesis occur in lymphoid tissues where HIV-1 is typically accompanied by infections with other pathogens (HIV co-pathogens). Co-pathogens greatly affect the clinical course of the disease and the transmission of HIV. The apicomplexan parasite Toxoplasma gondii is a common HIV co-pathogen associated with AIDS development. Here, we examined the interaction of T. gondii and HIV in coinfected human lymphoid tissue ex vivo. Both pathogens readily replicate in ex vivo infected blocks of human tonsillar tissue. Surprisingly, we found that live T. gondii preferentially inhibits R5 HIV-1 replication in coinfected tissues. This effect is reproduced by treatment of the tissue blocks with recombinant C-18, a T. gondii-encoded cyclophilin that binds to CCR5. These ex vivo findings raise the possibility that, in addition to being a co-factor in HIV disease, T. gondii may influence the outcome of viral infection by preferentially suppressing R5 variants.

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KW - Ex vivo

KW - HIV

KW - Human lymphoid tissue

KW - Toxoplasma gondii

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Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo

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Keywords

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