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M9480649.TXT
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1994-08-20
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Document 0649
DOCN M9480649
TI Differential replication and pathogenic effects of HIV-1 and HIV-2 in
Macaca nemestrina.
DT 9410
AU Otten RA; Brown BG; Simon M; Lupo LD; Parekh BS; Lairmore MD; Schable
CA; Schochetman G; Rayfield MA; Division of HIV/AIDS, Centers for
Disease Control and Prevention,; Atlanta, GA 30333.
SO AIDS. 1994 Mar;8(3):297-306. Unique Identifier : AIDSLINE GENBANK/L08465
AB OBJECTIVE: HIV-1 and HIV-2 isolates representing various geographic
regions and distinct viral subtypes were examined for their ability to
establish both in vitro and in vivo productive infections of Macaca
nemestrina (pigtail macaque) peripheral blood mononuclear cells.
METHODS: Animals were inoculated with either autologous cell-associated
or cell-free viral preparations of selected isolates. HIV-specific
immune responsiveness, hematologic changes, genetic variation, and virus
burden were monitored as delineators of HIV pathogenesis. RESULTS: HIV-2
replication in vitro and in vivo correlated with nascent antigen
production and rising viral titers as determined by infectious center
assays. Infection was detectable by polymerase chain reaction
amplification of proviral sequences in macaque cells as early as 1 week
postinoculation. Two distinct patterns of CD4+ cell depletion induced by
HIV-2 infection were observed during the first month postinoculation and
characterized by a moderate loss sustained through 20 weeks
postinoculation or a substantial loss maintained long-term (> 90 weeks).
Identity between inoculating viral stocks and subsequent viral isolates
from animals was established comparatively by limited sequence analysis
of specific domains within the HIV-2 pol and env genes. In contrast,
replication of HIV-1 isolates was limited or only semipermissive in
vitro. Intravenous inoculation of HIV-1 field isolates, using conditions
successful for HIV-2 (for example, identical viral titers), failed to
establish a productive viral infection leading to seroconversion of
fluctuations in hematologic cell markers. Infection with a high-titer
inoculum of a laboratory-adapted HIV-1 strain in vivo, as demonstrated
by polymerase chain reaction analysis, produced seroconversion in the
absence of overt viral replication or hematologic variations in one out
of four animals. CONCLUSIONS: This system provides for multifaceted
modeling of HIV pathogenesis, primarily with HIV-2 and potentially with
HIV-1/-2 chimerics, in support of immunotherapeutic developments and
critical evaluation of intervention practices.
DE Amino Acid Sequence Animal Base Sequence Comparative Study Disease
Models, Animal DNA Primers/GENETICS Gene Products, env/GENETICS Gene
Products, pol/GENETICS Human HIV Infections/*ETIOLOGY/MICROBIOLOGY
HIV-1/GENETICS/*PHYSIOLOGY/*PATHOGENICITY
HIV-2/GENETICS/*PHYSIOLOGY/*PATHOGENICITY Leukocytes,
Mononuclear/MICROBIOLOGY Macaca nemestrina Male Molecular Sequence
Data Species Specificity Support, U.S. Gov't, P.H.S.
Viremia/ETIOLOGY/MICROBIOLOGY *Virus Replication JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).