Packaging limits and stability of HIV-1 sequences in a coxsackievirus B vector.
Enteroviruses elicit protective mucosal immune responses that could be harnessed as part of a strategy to prevent sexual transmission of the human immunodeficiency virus-1 (HIV-1). We report the construction of replication-competent recombinant vectors of coxsackievirus B3 (CVB3) that express one or more portions of the HIV-1 Gag protein. Vectors containing the capsid domain of Gag were initially genetically unstable with protein expression lost after brief passage in tissue culture. Codon modification to increase the G/C content of the HIV-1 capsid sequence resulted in enhanced genetic stability of CVB3 vectors during in vitro passage. Cells infected with a vector expressing the matrix (MA) subunit of the HIV-1 Gag protein were susceptible to lysis by CD8 T cell clones specific for the SL9 epitope found within MA. These studies suggest that CVB3 vectors may be useful as vaccine vector candidates, if hurdles in class I antigen presentation and stability can be overcome.
Miller
John P
JP
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095, United States. johnmiller@mednet.ucla.edu
Geng
Yongzhi
Y
Ng
Hwee L
HL
Yang
Otto O
OO
Krogstad
Paul
P
D001482:Base Composition; D002460:Cell Line; D003062:Codon; D029822:Enterovirus B, Human / Q000235:genetics* / Q000502:physiology; D005822:Genetic Vectors; D042822:Genomic Instability; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D003062:Codon; D054301:gag Gene Products, Human Immunodeficiency Virus