Sequence diversity of SIVMne Nef in vivo and in vitro

Heidecker, Gisela; Muñoz, H.; Lloyd, Patricia A.; Hodge, David R.; Pei, G.-K.; Rick, Steven W.; Brehm, Katharina Erika Gerda; Ruscetti, Francis W.; Kuller, LaRene; Polacino, R.; Hu, Shiu Lok; Morton, William R.; Benveniste, R E

doi:10.1111/j.1600-0684.1998.tb00229.x

Cited by 2 publications

(2 citation statements)

References 32 publications

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“…Plasmids and mutagenesis SIV(Mne) was originally isolated on HuT 78 cells from a pig-tailed macaque (Macaca nemestrina) with lymphoma [2]. A single-cell clone of infected HuT 78 cells, E11S, which produces infections virus containing high levels of gp120 SU [4], was used as the source of DNA to obtain the fulllength proviral clone, SIV(Mne) clone 8 [17,18]. Clone 8 is flanked on both the 3% and 5% ends by approximately 1 kbp of HuT 78 cellular DNA.…”

Section: Methodsmentioning

confidence: 99%

Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination*

Gorelick

Lifson

Yovandich

et al. 2000

J of Medical Primatology

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A simian immunodeficiency virus (SIV)(Mne) DNA clone was constructed that produces viruses containing a four amino acid deletion in the second zinc finger of the nucleocapsid (NC) domain of the Gag polyprotein. Viruses produced from this clone, although non-infectious both in vitro and in vivo, complete a majority of the steps in a single retroviral infection cycle. Eight pig-tailed macaques (Macaca nemestrina) were inoculated intramuscularly and subcutaneously three times over the course of 24 weeks with the NC mutant expressing DNA. These macaques, and four controls, were then challenged mucosally (intrarectally) with the homologous virus (SIV Mne CL E11S) and monitored for evidence of infection and clinical disease. Prior to challenge, a measurable humoral immune response was noted in four of eight immunized macaques. After challenge, all 12 macaques became infected, although four immunized animals greatly restricted their viral replication, and one immunized animal that controlled replication remains antibody negative. No disease has been evidence during the 46-week period of monitoring after challenge.

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Section: Methodsmentioning

confidence: 99%

Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination*

Gorelick

Lifson

Yovandich

et al. 2000

J of Medical Primatology

View full text Add to dashboard Cite

show abstract

“…SIV(Mne), originally isolated from a pig-tailed macaque (Macaca nemestrina) with lymphoma, was cultured in HuT 78 cells (6). A single cell clone of infected HuT 78 cells, E11S, was used as the source of DNA to obtain the full-length proviral clone, SIV(Mne) clone 8 (7,33). Clone 8 is flanked on both the 3Ј and 5Ј ends by approximately 1 kbp of uncharacterized cellular DNA from the HuT 78 cells.…”

Section: Methodsmentioning

confidence: 99%

Protection of Macaca nemestrina from Disease following Pathogenic Simian Immunodeficiency Virus (SIV) Challenge: Utilization of SIV Nucleocapsid Mutant DNA Vaccines with and without an SIV Protein Boost

Gorelick

Benveniste

Lifson

et al. 2000

J Virol

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Molecular clones were constructed that express nucleocapsid (NC) deletion mutant simian immunodeficiency viruses (SIVs) that are replication defective but capable of completing virtually all of the steps of a single viral infection cycle. These steps include production of particles that are viral RNA deficient yet contain a full complement of processed viral proteins. The mutant particles are ultrastructurally indistinguishable from wild-type virus. Similar to a live attenuated vaccine, this approach should allow immunological presentation of a full range of viral epitopes, without the safety risks of replicating virus. A total of 11 Macaca nemestrina macaques were inoculated with NC mutant SIV expressing DNA, intramuscularly (i.m.) in one study and i.m. and subcutaneously in another study. Six control animals received vector DNA lacking SIV sequences. Only modest and inconsistent humoral responses and no cellular immune responses were observed prior to challenge. Following intravenous challenge with 20 animal infectious doses of the pathogenic SIV(Mne) in a long-term study, all control animals became infected and three of four animals developed progressive SIV disease leading to death. All 11 NC mutant SIV DNA-immunized animals became infected following challenge but typically showed decreased initial peak plasma SIV RNA levels compared to those of control animals (P ‫؍‬ 0.0007). In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4 ؉ T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation. Although a subset of immunized and control animals were boosted with SIV(Mne) proteins, no apparent protective benefit was observed. Immunization of macaques with DNA that codes for replication-defective but structurally complete virions appears to protect from or at least delay the onset of AIDS after infection with a pathogenic immunodeficiency virus. With further optimization, this may be a promising approach for vaccine development.The overwhelming majority of human viral vaccines used clinically consist of either inactivated whole virus particles or live attenuated viruses. Attenuated viruses have proven to be the most effective vaccines for humans. Additionally, macaques infected with simian immunodeficiency virus (SIV) strains attenuated for in vivo virulence by deletion of the nef gene or other regulatory sequences have been shown previously to be protected from challenge with pathogenic SIV (1, 5, 12, 16-21, 30, 32, 38-40, 46, 49, 50, 55, 56, 59). Indeed, attenuated SIV strains are generally accepted as being among the most effective vaccines evaluated to date in nonhuman primate models (34). However, a major concern with attenuated virus vaccines is safety. This is especially true for viruses such as human immunodeficiency virus (HIV) or SIV that have a high mutation rate and integrate into the host's genome and for which the outcome of a pathogenic infection is potentially lethal. With the advent of ...

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Sequence diversity of SIV_Mne Nef in vivo and in vitro

Cited by 2 publications

References 32 publications

Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination*

Mucosal challenge of Macaca nemestrina with simian immunodeficiency virus (SIV) following SIV nucleocapsid mutant DNA vaccination*

Protection of Macaca nemestrina from Disease following Pathogenic Simian Immunodeficiency Virus (SIV) Challenge: Utilization of SIV Nucleocapsid Mutant DNA Vaccines with and without an SIV Protein Boost

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