Pseudotyping of HIV-1 with human Tlymphotropic virus 1 (HTLV-1) envelope glycoprotein during HIV-1-HTLV-1 coinfection facilitates direct HIV-1 infection of female genital epithelial cells

Implications for sexual transmission of HIV-1

Yuyang Tang, Alvin M. George, Oksana Petrechko, Franklin J. Nouvet, Stephanie D. Sweet, Yuetsu Tanaka, Brian S. Imbiakha, Guochun Jiang, Wei Gao, Kathryn Anastos, James E.K. Hildretha

Research output: Contribution to journalArticle

Abstract

Female genital epithelial cells cover the genital tract and provide the first line of protection against infection with sexually transmitted pathogenic viruses. These cells normally are impervious to HIV-1. We report that coinfection of cells by HIV-1 and another sexually transmitted virus, human T-lymphotropic virus 1 (HTLV- 1), led to production of HIV-1 that had expanded cell tropism and was able to directly infect primary vaginal and cervical epithelial cells. HIV-1 infection of epithelial cells was blocked by neutralizing antibodies against the HTLV-1 envelope (Env) protein, indicating that the infection was mediated through HTLV-1 Env pseudotyping of HIV-1. Active replication of HIV-1 in epithelial cells was demonstrated by inhibition with anti-HIV-1 drugs. We demonstrated that HIV-1 derived from peripheral blood of HIV-1-HTLV-1-coinfected subjects could infect primary epithelial cells in an HTLV-1 Env-dependent manner. HIV-1 from subjects infected with HIV-1 alone was not able to infect epithelial cells. These results indicate that pseudotyping of HIV-1 with HTLV-1 Env can occur in vivo. Our data further reveal that active replication of both HTLV-1 and HIV-1 is required for production of pseudotyped HIV-1. Our findings indicate that pseudotyping of HIV-1 with HTLV-1 Env in coinfected cells enabled HIV-1 to directly infect nonpermissive female genital epithelial cells. This phenomenon may represent a risk factor for enhanced sexual transmission of HIV-1 in regions where virus coinfection is common.

Original languageEnglish (US)
Article numbere00038-18
JournalmSphere
Volume3
Issue number2
DOIs
StatePublished - Mar 1 2018

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Coinfection
HIV Infections
HIV-1
Glycoproteins
Epithelial Cells
Viruses
Viral Envelope Proteins
Anti-HIV Agents
Human T-lymphotropic virus 1
Tropism
Sexually Transmitted Diseases
Neutralizing Antibodies

Keywords

  • Envelope glycoprotein
  • Epithelial cells
  • Human immunodeficiency virus
  • Human T-cell leukemia virus
  • Primary T-cells
  • Pseudotype
  • Retroviruses
  • Sexual transmission
  • Virus tropism

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Pseudotyping of HIV-1 with human Tlymphotropic virus 1 (HTLV-1) envelope glycoprotein during HIV-1-HTLV-1 coinfection facilitates direct HIV-1 infection of female genital epithelial cells : Implications for sexual transmission of HIV-1. / Tang, Yuyang; George, Alvin M.; Petrechko, Oksana; Nouvet, Franklin J.; Sweet, Stephanie D.; Tanaka, Yuetsu; Imbiakha, Brian S.; Jiang, Guochun; Gao, Wei; Anastos, Kathryn; Hildretha, James E.K.

In: mSphere, Vol. 3, No. 2, e00038-18, 01.03.2018.

Research output: Contribution to journalArticle

Tang, Yuyang ; George, Alvin M. ; Petrechko, Oksana ; Nouvet, Franklin J. ; Sweet, Stephanie D. ; Tanaka, Yuetsu ; Imbiakha, Brian S. ; Jiang, Guochun ; Gao, Wei ; Anastos, Kathryn ; Hildretha, James E.K. / Pseudotyping of HIV-1 with human Tlymphotropic virus 1 (HTLV-1) envelope glycoprotein during HIV-1-HTLV-1 coinfection facilitates direct HIV-1 infection of female genital epithelial cells : Implications for sexual transmission of HIV-1. In: mSphere. 2018 ; Vol. 3, No. 2.
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abstract = "Female genital epithelial cells cover the genital tract and provide the first line of protection against infection with sexually transmitted pathogenic viruses. These cells normally are impervious to HIV-1. We report that coinfection of cells by HIV-1 and another sexually transmitted virus, human T-lymphotropic virus 1 (HTLV- 1), led to production of HIV-1 that had expanded cell tropism and was able to directly infect primary vaginal and cervical epithelial cells. HIV-1 infection of epithelial cells was blocked by neutralizing antibodies against the HTLV-1 envelope (Env) protein, indicating that the infection was mediated through HTLV-1 Env pseudotyping of HIV-1. Active replication of HIV-1 in epithelial cells was demonstrated by inhibition with anti-HIV-1 drugs. We demonstrated that HIV-1 derived from peripheral blood of HIV-1-HTLV-1-coinfected subjects could infect primary epithelial cells in an HTLV-1 Env-dependent manner. HIV-1 from subjects infected with HIV-1 alone was not able to infect epithelial cells. These results indicate that pseudotyping of HIV-1 with HTLV-1 Env can occur in vivo. Our data further reveal that active replication of both HTLV-1 and HIV-1 is required for production of pseudotyped HIV-1. Our findings indicate that pseudotyping of HIV-1 with HTLV-1 Env in coinfected cells enabled HIV-1 to directly infect nonpermissive female genital epithelial cells. This phenomenon may represent a risk factor for enhanced sexual transmission of HIV-1 in regions where virus coinfection is common.",
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T2 - Implications for sexual transmission of HIV-1

AU - Tang, Yuyang

AU - George, Alvin M.

AU - Petrechko, Oksana

AU - Nouvet, Franklin J.

AU - Sweet, Stephanie D.

AU - Tanaka, Yuetsu

AU - Imbiakha, Brian S.

AU - Jiang, Guochun

AU - Gao, Wei

AU - Anastos, Kathryn

AU - Hildretha, James E.K.

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N2 - Female genital epithelial cells cover the genital tract and provide the first line of protection against infection with sexually transmitted pathogenic viruses. These cells normally are impervious to HIV-1. We report that coinfection of cells by HIV-1 and another sexually transmitted virus, human T-lymphotropic virus 1 (HTLV- 1), led to production of HIV-1 that had expanded cell tropism and was able to directly infect primary vaginal and cervical epithelial cells. HIV-1 infection of epithelial cells was blocked by neutralizing antibodies against the HTLV-1 envelope (Env) protein, indicating that the infection was mediated through HTLV-1 Env pseudotyping of HIV-1. Active replication of HIV-1 in epithelial cells was demonstrated by inhibition with anti-HIV-1 drugs. We demonstrated that HIV-1 derived from peripheral blood of HIV-1-HTLV-1-coinfected subjects could infect primary epithelial cells in an HTLV-1 Env-dependent manner. HIV-1 from subjects infected with HIV-1 alone was not able to infect epithelial cells. These results indicate that pseudotyping of HIV-1 with HTLV-1 Env can occur in vivo. Our data further reveal that active replication of both HTLV-1 and HIV-1 is required for production of pseudotyped HIV-1. Our findings indicate that pseudotyping of HIV-1 with HTLV-1 Env in coinfected cells enabled HIV-1 to directly infect nonpermissive female genital epithelial cells. This phenomenon may represent a risk factor for enhanced sexual transmission of HIV-1 in regions where virus coinfection is common.

AB - Female genital epithelial cells cover the genital tract and provide the first line of protection against infection with sexually transmitted pathogenic viruses. These cells normally are impervious to HIV-1. We report that coinfection of cells by HIV-1 and another sexually transmitted virus, human T-lymphotropic virus 1 (HTLV- 1), led to production of HIV-1 that had expanded cell tropism and was able to directly infect primary vaginal and cervical epithelial cells. HIV-1 infection of epithelial cells was blocked by neutralizing antibodies against the HTLV-1 envelope (Env) protein, indicating that the infection was mediated through HTLV-1 Env pseudotyping of HIV-1. Active replication of HIV-1 in epithelial cells was demonstrated by inhibition with anti-HIV-1 drugs. We demonstrated that HIV-1 derived from peripheral blood of HIV-1-HTLV-1-coinfected subjects could infect primary epithelial cells in an HTLV-1 Env-dependent manner. HIV-1 from subjects infected with HIV-1 alone was not able to infect epithelial cells. These results indicate that pseudotyping of HIV-1 with HTLV-1 Env can occur in vivo. Our data further reveal that active replication of both HTLV-1 and HIV-1 is required for production of pseudotyped HIV-1. Our findings indicate that pseudotyping of HIV-1 with HTLV-1 Env in coinfected cells enabled HIV-1 to directly infect nonpermissive female genital epithelial cells. This phenomenon may represent a risk factor for enhanced sexual transmission of HIV-1 in regions where virus coinfection is common.

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KW - Human immunodeficiency virus

KW - Human T-cell leukemia virus

KW - Primary T-cells

KW - Pseudotype

KW - Retroviruses

KW - Sexual transmission

KW - Virus tropism

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