       Document 0389
 DOCN  M9620389
 TI    Persistent infection of macaques with simian-human immunodeficiency
       viruses.
 DT    9602
 AU    Li JT; Halloran M; Lord CI; Watson A; Ranchalis J; Fung M; Letvin NL;
       Sodroski JG; Dana-Farber Cancer Institute, Department of Pathology,
       Harvard; Medical School, Boston, Massachusetts, USA.
 SO    J Virol. 1995 Nov;69(11):7061-7. Unique Identifier : AIDSLINE
       MED/96013809
 AB    Chimeric simian-human immunodeficiency viruses (SHIV) containing the
       human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some
       cases, vpu genes were inoculated into eight cynomolgus monkeys. Viruses
       could be consistently recovered from the CD8-depleted peripheral blood
       lymphocytes of all eight animals for at least 2 months. After this time,
       virus isolation varied among the animals, with viruses continuing to be
       isolated from some animals beyond 600 days after inoculation. The level
       of viral RNA in plasma during acute infection and the frequency of virus
       isolation after the initial 2-month period were higher for the
       Vpu-positive viruses. All of the animals remained clinically healthy,
       and the absolute numbers of CD4-positive lymphocytes were stable.
       Antibodies capable of neutralizing HIV-1 were generated at high titers
       in animals exhibiting the greatest consistency of virus isolation.
       Strain-specific HIV-1-neutralizing antibodies were initially elicited,
       and then more broadly neutralizing antibodies were elicited. env
       sequences from two viruses isolated more than a year after infection
       were analyzed. In the Vpu-negative SHIV, for which virus loads were
       lower, a small amount of env variation, which did not correspond to that
       found in natural HIV-1 variants, was observed. By contrast, in the
       Vpu-positive virus, which was consistently isolated from the host
       animal, extensive variation of the envelope glycoproteins in the defined
       variable gp120 regions was observed. Escape from neutralization by CD4
       binding site monoclonal antibodies was observed for the viruses with the
       latter envelope glycoproteins, and the mechanism of escape appears to
       involve decreased binding of the antibody to the monomeric gp120
       glycoproteins. The consistency with which SHIV infection of cynomolgus
       monkeys is initiated and the similarities in the neutralizing antibody
       response to SHIV and HIV-1 support the utility of this model system for
       the study of HIV-1 prophylaxis.
 DE    Acquired Immunodeficiency Syndrome/BLOOD/IMMUNOLOGY/*VIROLOGY  Amino
       Acid Sequence  Animal  Antibodies, Viral/BLOOD  Antibody Formation  Base
       Sequence  Chimera  DNA Primers  DNA, Viral/ANALYSIS  Genes, env  Genes,
       rev  Genes, tat  Genes, vpu  Human  HIV/*GENETICS/ISOLATION &
       PURIF/*PATHOGENICITY  HIV Antibodies/BLOOD  HIV Envelope Protein
       gp120/IMMUNOLOGY  Lymphocytes/*VIROLOGY  Macaca fascicularis  Molecular
       Sequence Data  Point Mutation  Polymerase Chain Reaction  RNA,
       Viral/BLOOD  Simian Acquired Immunodeficiency Syndrome/BLOOD/IMMUNOLOGY/
       *VIROLOGY  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       SIV/*GENETICS/ISOLATION & PURIF/*PATHOGENICITY  Time Factors  Viral
       Envelope Proteins/GENETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

