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Pathogenesis and Immunity

A Period of Transient Viremia and Occult Infection Precedes Persistent Viremia and Antiviral Immune Responses during Multiple Low-Dose Intravaginal Simian Immunodeficiency Virus Inoculations

Zhong-Min Ma, Kristina Abel, Tracy Rourke, Yichuan Wang, Christopher J. Miller
Zhong-Min Ma
1California National Primate Research Center
2Center for Comparative Medicine
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Kristina Abel
1California National Primate Research Center
2Center for Comparative Medicine
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Tracy Rourke
2Center for Comparative Medicine
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Yichuan Wang
1California National Primate Research Center
2Center for Comparative Medicine
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Christopher J. Miller
1California National Primate Research Center
2Center for Comparative Medicine
3Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine
4Division of Infectious Diseases, School of Medicine, University of California Davis, Davis, California
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  • For correspondence: cjmiller@ucdavis.edu
DOI: 10.1128/JVI.78.24.14048-14052.2004
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    FIG. 1.

    Plasma SIV vRNA levels during multiple IVAG inoculation series with a low dose of SIVmac251. Week 13 was the end of the inoculation series. PI, postinfection.

Tables

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  • TABLE 1.

    Virologic analysis of peripheral blood samples from monkeys inoculated IVAG multiple times with a low dose of SIVmac251

    Animal and assayResult at following time (wk) after first inoculation:
    012345678910111213c14
    29029
        vDNAa−+−++++++++++++
        Virus isolation−−−−+++++++++++
        vRNAb−−5.07.47.36.86.66.36.46.56.66.76.86.87.0
    27361
        vDNA−−+++++++++++++
        Virus isolation−−−−+++++++++++
        vRNA−−5.76.67.06.26.15.65.75.65.85.65.35.45.0
    25479
        vDNA−−−+−+++−++++−+
        Virus isolation−−−−−++++++++++
        vRNA−−−−−6.48.37.87.87.97.77.87.88.08.3
    29459
        vDNA−−−+−−+++++++++
        Virus isolation−−−−−−−−+++++++
        vRNA−−−−−−2.14.98.17.57.37.37.57.77.9
    25948
        vDNA−−−−−++++++++++
        Virus isolation−−−−−+++++++++−
        vRNA−−−−−5.37.26.45.24.84.74.34.24.34.5
    25908
        vDNA−−−−+−−++++++++
        Virus isolation−−−−−−−−++++++−
        vRNA−−−−−−−4.57.66.05.85.75.35.35.3
    26811
        vDNA−−−+−−−+−+−++++
        Virus isolation−−−−−−−++++++++
        vRNA−−−−−2.33.17.47.06.55.96.25.96.16.2
    26513
        vDNA−+−−−−−−+++++++
        Virus isolation−−−−−−−−−−+++++
        vRNA−−−−2.9−−−−4.57.16.96.05.85.8
    • ↵ a SIVgag nested PCR assay. + indicates vDNA detected in PBMC (106 PBMC tested at each time point).

    • ↵ b Plasma vRNA level (log10 copies per milliliter).

    • ↵ c Final inoculation in series.

  • TABLE 2.

    Anti-SIV immune responses in peripheral blood and CVS from monkeys IVAG inoculated multiple times with a low dose of SIVmac251

    Animal and assayResult at following time (wk) after first inoculation:
    01234567891011121314
    29029
        T-cell proliferationa−−d−−−4.62.1−−−−8.14.515.54.8
        ELISPOTb−−−−−−−−
        Plasma IgGc−−−4,00010,00020,000200,000200,000400,000200,000
        CVS IgGc−−−−−8080160160320
        CVS IgAc−−−2224222
    27361
        T-cell proliferation−−−d−−−−−−−165−11.34.539.3
        ELISPOT−−−5022070175125
        Plasma IgG−−−−−1,0004,00020,000200,000200,000800,000320,000
        CVS IgG−−−−−80160160160320
        CVS IgA−−−−−44444
    25479
        T-cell proliferation−−−9.9d2.9−2.5−−−−3.12.5−−
        ELISPOT−−−−−−−−
        Plasma IgG−−−−−−−−−−100100
        CVS IgG−−−−−−−−−
        CVS IgA−−−−−−−−−−
    29459
        T-cell proliferation−−−−d−−8.5−−−−−−11.13.2
        ELISPOT−−−−−−−−
        Plasma IgG−−−−−−−−2004,0004,0001002,000
        CVS IgG−−−−−−−−−−
        CVS IgA−−−−−−−−−1
    25948
        T-cell proliferation−−−2.7−−d2.66.53.93.046.020.126.737.535.9
        ELISPOT−−70−−−225170
        Plasma IgG−−−−−1002,0002,00016,00016,000160,000
        CVS IgG−−−−−223240320
        CVS IgA−−−−111222
    25908
        T-cell proliferation−−−−−d2.14.23.1−−−−2.34.53.6
        ELISPOT−−130−−−−−
        Plasma IgG−−−−−−2004,00010,000100,000160,000
        CVS IgG−−−−−−81010
        CVS IgA−−−−−−−222
    26811
        T-cell proliferation−−−−d−−−−−−9.0−−2.1−
        ELISPOT−−95−40−−−
        Plasma IgG−−−−−−1002004004008,000
        CVS IgG−−−−−−−−220
        CVS IgA−−−−−−−−−−
    26513
        T-cell proliferation−−d20.92.82.63.7−−−−2.7−−2.6
        ELISPOT−−−−−−110−
        Plasma IgG−−−−−−−−10040080,000
        CVS IgG−−−−−−−−−−
        CVS IgA−−−−−−−−−−
    • ↵ a AT-2 SIV T-cell proliferation assay results are shown as a stimulation index. A minus sign indicates a stimulation index of ≤2.

    • ↵ b SIV gag-specific IFN-γ ELISPOT assay results are shown as the number of spot-forming cells per 106 PBMC. The number of background spots in medium-only wells was subtracted from the number of spots in peptide-stimulated wells.

    • ↵ c Detergent-disrupted SIV ELISA results are shown as the reciprocal of the highest positive dilution that was above the cutoff.

    • ↵ d First PBMC sample in an animal that was vDNA positive by nested PCR for SIVgag.

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A Period of Transient Viremia and Occult Infection Precedes Persistent Viremia and Antiviral Immune Responses during Multiple Low-Dose Intravaginal Simian Immunodeficiency Virus Inoculations
Zhong-Min Ma, Kristina Abel, Tracy Rourke, Yichuan Wang, Christopher J. Miller
Journal of Virology Nov 2004, 78 (24) 14048-14052; DOI: 10.1128/JVI.78.24.14048-14052.2004

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A Period of Transient Viremia and Occult Infection Precedes Persistent Viremia and Antiviral Immune Responses during Multiple Low-Dose Intravaginal Simian Immunodeficiency Virus Inoculations
Zhong-Min Ma, Kristina Abel, Tracy Rourke, Yichuan Wang, Christopher J. Miller
Journal of Virology Nov 2004, 78 (24) 14048-14052; DOI: 10.1128/JVI.78.24.14048-14052.2004
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  • Top
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    • ABSTRACT
    • Systemic SIV infection following multiple low-dose IVAG SIVmac251 inoculations.
    • Anti-SIV immune responses in multiple low-dose IVAG-inoculated rhesus monkeys.
    • ACKNOWLEDGMENTS
    • FOOTNOTES
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KEYWORDS

Simian Acquired Immunodeficiency Syndrome
simian immunodeficiency virus
Vagina
Viremia

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