Simian/human immunodeficiency virus(89.6) expressing the chemokine genes MIP-1alpha, RANTES, or lymphotactin.
We constructed replication competent, attenuated, nef-deleted SHIV(89.6) that express the rhesus macaque chemokine genes MIP-1alpha, RANTES, or LTN from the nef region. The chemokine inserts were stable during several passages in CEMx174 cells and the viruses grew well in activated rhesus PBMC. Expression of virally encoded MIP-1alpha, RANTES, or LTN was detected in culture fluids from infected HOS CD4(+) CXCR4(+) cells, that were used because they have a low background production of these chemokines. The in vitro growth kinetics of all nef-deleted SHIV(89.6) were slower than the parental strain in both CEMx174 cells and rhesus PBMC. Rhesus macaques were susceptible to SHIV(89.6-MIP-1alpha), SHIV(89.6-RANTES), SHIV(89.6-LTN), and nef-deleted control SHIV(89.6-dLTN) infection via the intrarectal route using standard virus doses, and intact viruses were reisolated from infected animals throughout the interval of acute infection. SHIV expressing the chemokine genes MIP-1alpha, RANTES, or LTN may help determine the in vivo roles for these chemokines in modulating virus replication and disease.
Institute of Human Virology, University of Maryland, Biotechnology Institute, Baltimore, Maryland, USA.
Paul M
PM
Waterman
Moiz
M
Kitabwalla
Ilia
I
Tikhonov
C David
CD
Pauza
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D019744:Chemokines, C; D003001:Cloning, Molecular; D017353:Gene Deletion; D015693:Gene Products, nef / Q000235:genetics; D006678:HIV / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D015658:HIV Infections / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008253:Macaca mulatta; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019744:Chemokines, C; D015693:Gene Products, nef; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C018997:lymphotactin; D054311:nef Gene Products, Human Immunodeficiency Virus