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).