Recombinant vesicular stomatitis viruses encoding simian immunodeficiency virus receptors target infected cells and control infection.
We have constructed VSV recombinants lacking the viral glycoprotein gene and instead expressing rhesus macaque SIV receptors CD4 and CCR5 with or without the receptor DC-SIGN. The recombinant expressing CD4 and CCR5 specifically infected SIV envelope protein-expressing cells. Incorporation of DC-SIGN into the particles required deletion of the cytoplasmic domain. Inclusion of DC-SIGN in the particles definitely enhanced infection, indicating that the enhancement by coexpression of DC-SIGN with CD4 and CCR5 does not require internalization of the virus into cells. The recombinants also specifically infected, killed, and propagated in CEMx174 cells that were first infected with an SIV expressing EGFP. If cells were superinfected with either of the recombinants after the primary SIV infection, the numbers of SIV-infected cells and titers of infectious SIV in the cultures were significantly reduced. Such antivirals can now be tested in the SIV/non-human primate model for AIDS to determine their therapeutic value in vivo.
Okuma
Kazu
K
Department of Pathology (LH 302/315C), Yale University School of Medicine, 310 Cedar St., New Haven, CT 06510, USA.
Boritz
Eli
E
Walker
Jason
J
Sarkar
Aishawarya
A
Alexander
Louis
L
Rose
John K
JK
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D005822:Genetic Vectors; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin