Blocking HIV-1 infection by chromosomal integrative expression of human CD4 on the surface of lactobacillus acidophilus ATCC 4356

Wenzhong Wei, Joshua Wiggins, Duoyi Hu, Vladimir Vrbanac, Dane Bowder, Michael Mellon, Andrew Tager, Joseph Sodroski, Shi Hua Xiang

Research output: Contribution to journalArticle

Abstract

Lactobacillus bacteria are potential delivery vehicles for biopharmaceutical molecules because they are well-recognized as safe microorganisms that naturally inhabit the human body. The goal of this study was to employ these lactobacilli to combat human immunodeficiency virus type 1 (HIV-1) infection and transmission. By using a chromosomal integration method, we engineered Lactobacillus acidophilus ATCC 4356 to display human CD4, the HIV-1 receptor, on the cell surface. Since human CD4 can bind to any infectious HIV-1 particles, the engineered lactobacilli can potentially capture HIV-1 of different subtypes and prevent infection. Our data demonstrate that the CD4-carrying bacteria are able to adsorb HIV-1 particles and reduce infection significantly in vitro and also block intrarectal HIV-1 infection in a humanized mouse model in preliminary tests in vivo. Our results support the potential of this approach to decrease the efficiency of HIV-1 sexual transmission. IMPORTANCE In the absence of an effective vaccine, alternative approaches to block HIV-1 infection and transmission with commensal bacteria expressing antiviral proteins are being considered. This report provides a proof-of-concept by using Lactobacillus bacteria stably expressing the HIV-1 receptor CD4 to capture and neutralize HIV-1 in vitro and in a humanized mouse model. The stable expression of antiviral proteins, such as CD4, following genomic integration of the corresponding genes into this Lactobacillus strain may contribute to the prevention of HIV-1 sexual transmission.

Original languageEnglish (US)
Article numberY
JournalJournal of virology
Volume93
Issue number8
DOIs
StatePublished - Jan 1 2019

Fingerprint

Lactobacillus acidophilus
Virus Diseases
Human immunodeficiency virus 1
HIV-1
Lactobacillus
infection
antiviral proteins
Bacteria
Virus Receptors
Infectious Disease Transmission
bacteria
Virion
Antiviral Agents
animal models
biopharmaceuticals
receptors
Infection
Human Body
Proteins
Vaccines

Keywords

  • Bacterial engineering
  • CD4
  • Chromosomal integrative expression
  • HIV infection
  • Humanized mice
  • Lactobacillus acidophilus ATCC 4356

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Blocking HIV-1 infection by chromosomal integrative expression of human CD4 on the surface of lactobacillus acidophilus ATCC 4356. / Wei, Wenzhong; Wiggins, Joshua; Hu, Duoyi; Vrbanac, Vladimir; Bowder, Dane; Mellon, Michael; Tager, Andrew; Sodroski, Joseph; Xiang, Shi Hua.

In: Journal of virology, Vol. 93, No. 8, Y, 01.01.2019.

Research output: Contribution to journalArticle

Wei, Wenzhong ; Wiggins, Joshua ; Hu, Duoyi ; Vrbanac, Vladimir ; Bowder, Dane ; Mellon, Michael ; Tager, Andrew ; Sodroski, Joseph ; Xiang, Shi Hua. / Blocking HIV-1 infection by chromosomal integrative expression of human CD4 on the surface of lactobacillus acidophilus ATCC 4356. In: Journal of virology. 2019 ; Vol. 93, No. 8.
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