title: Blocking of α4β7 gut-homing integrin during acute infection leads to decreased plasma and gastrointestinal tissue viral loads in simian immunodeficiency virus-infected rhesus macaques.
abstract: Intravenous administration of a novel recombinant rhesus mAb against the α4β7 gut-homing integrin (mAb) into rhesus macaques just prior to and during acute SIV infection resulted in significant decrease in plasma and gastrointestinal (GI) tissue viral load and a marked reduction in GI tissue proviral DNA load as compared with control SIV-infected rhesus macaques. This mAb administration was associated with increases in peripheral blood naive and central memory CD4(+) T cells and maintenance of a high frequency of CCR5(+)CD4(+) T cells. Additionally, such mAb administration inhibited the mobilization of NK cells and plasmacytoid dendritic cells characteristically seen in the control animals during acute infection accompanied by the inhibition of the synthesis of MIP-3α by the gut tissues. These data in concert suggest that blocking of GI trafficking CD4(+) T cells and inhibiting the mobilization of cell lineages of the innate immune system may be a powerful new tool to protect GI tissues and modulate acute lentiviral infection.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. pathaaa@emory.edu
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Keith A
authors.initials: KA
authors.lastname: Reimann
authors.forename: Ann E
authors.initials: AE
authors.lastname: Mayne
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Susan T
authors.initials: ST
authors.lastname: Stephenson
authors.forename: Rijian
authors.initials: R
authors.lastname: Wang
authors.forename: Xinyue
authors.initials: X
authors.lastname: Wang
authors.forename: Jichu
authors.initials: J
authors.lastname: Li
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Price
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Little
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zaidi
authors.forename: Robert
authors.initials: R
authors.lastname: Lyles
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
mesh_terms: D000208:Acute Disease; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage*; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000097:blood; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007275:Injections, Intravenous; D039441:Integrin alpha4 / Q000097:blood / Q000276:immunology; D039641:Integrin beta Chains / Q000097:blood / Q000276:immunology; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008253:Macaca mulatta; D021381:Protein Transport / Q000276:immunology; D011533:Proviruses / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D019562:Viral Load / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D004279:DNA, Viral; D039641:Integrin beta Chains; D016023:Integrins; D014614:Vaccines, Synthetic; C071777:integrin alpha4beta7; C091368:integrin beta7; D039441:Integrin alpha4