Abstract

A unique live attenuated simian immunodeficiency virus that encodes the capability to excise its integrated proviral genome from the infected cell's genome after limited rounds of virus replication was generated. This attenuated virus strain contains four specific mutations in its proviral genome. First, the 3' long terminal repeat (LTR) contains an engineered IoxP site. Second, the ATG codons of nef gene that overlap with gp41 was mutated to abolish the translation start codons. Third, the non-overlapping region of nef between gp41 and the 3' LTR was excised and replaced with a minimal DNA segment containing a unique Mlu1 restriction endonuclease site. Lastly, DNA encoding the bacteriophage P1 cre recombinase gene was cloned into the unique Mlu1 site within the proviral genome. Since this gene is flanked by unique Mlu1 restriction endonuclease sites, the cre recombinase gene was positioned in either the sense or antisense orientation. Live attenuated viruses such as these have not been generated or proposed by others in the field of acquired immunodeficiency syndrome (AIDS) research. Extensive evaluation of unique live attenuated vaccines of SIV in rhesus macaques may provide the means for creating a safe, effective, live attenuated vaccine to protect against AIDS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-37
Application #
5219760
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
37
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Slayden, Ov Daniel; Friason, Francis Kathryn E; Bond, Kise Rosen et al. (2018) Hormonal regulation of oviductal glycoprotein 1 (OVGP1; MUC9) in the rhesus macaque cervix. J Med Primatol 47:362-370
Okoye, Afam A; Hansen, Scott G; Vaidya, Mukta et al. (2018) Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat Med 24:1430-1440
Jensen, Jeffrey T; Hanna, Carol; Mishler, Emily et al. (2018) Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons. J Med Primatol 47:40-45
Toro, C A; Aylwin, C F; Lomniczi, A (2018) Hypothalamic epigenetics driving female puberty. J Neuroendocrinol 30:e12589
Bulgarelli, Daiane L; Ting, Alison Y; Gordon, Brenda J et al. (2018) Development of macaque secondary follicles exposed to neutral red prior to 3-dimensional culture. J Assist Reprod Genet 35:71-79
Prola-Netto, Joao; Woods, Mark; Roberts, Victoria H J et al. (2018) Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure. Radiology 286:122-128
Moccetti, Federico; Brown, Eran; Xie, Aris et al. (2018) Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries. J Am Coll Cardiol 72:1015-1026
Blue, Steven W; Winchell, Andrea J; Kaucher, Amy V et al. (2018) Simultaneous quantitation of multiple contraceptive hormones in human serum by LC-MS/MS. Contraception 97:363-369
Jeon, Sookyoung; Li, Qiyao; Rubakhin, Stanislav S et al. (2018) 13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study. Nutr Res :
Dissen, G A; Adachi, K; Lomniczi, A et al. (2017) Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update. Reprod Domest Anim 52 Suppl 2:354-358

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