       Document 0787
 DOCN  M9590787
 TI    Viral factors determine progression to AIDS in simian immunodeficiency
       virus-infected newborn rhesus macaques.
 DT    9509
 AU    Marthas ML; van Rompay KK; Otsyula M; Miller CJ; Canfield DR; Pedersen
       NC; McChesney MB; California Regional Primate Research Center,
       University of; California, Davis 95616, USA.
 SO    J Virol. 1995 Jul;69(7):4198-205. Unique Identifier : AIDSLINE
       MED/95287472
 AB    To evaluate how viral variants may affect disease progression in human
       pediatric AIDS, we studied the potential of three simian
       immunodeficiency virus (SIV) isolates to induce simian AIDS in newborn
       rhesus macaques. The three virus isolates were previously shown to range
       from pathogenic (SIVmac251 and SIVmac239) to nonpathogenic (SIVmac1A11)
       when inoculated intravenously into juvenile and adult rhesus macaques.
       Six newborn macaques inoculated with pathogenic, uncloned SIVmac251
       developed persistent, high levels of cell-associated and cell-free
       viremia, had no detectable antiviral antibodies, and had poor weight
       gain; these animals all exhibited severe clinical disease and pathologic
       lesions diagnostic for simian AIDS and were euthanatized 10 to 26 weeks
       after inoculation. Two newborns inoculated with pathogenic, molecularly
       cloned SIVmac239 developed persistent high virus load in peripheral
       blood, but both animals had normal weight gain and developed antiviral
       antibodies. One of the SIVmac239-infected neonates exhibited pathologic
       lesions diagnostic for SAIDS and was euthanatized at 34 weeks after
       inoculation; the other SIVmac239-infected neonate remained alive and
       exhibited no significant clinical disease for more than 1 year after
       inoculation. In contrast, three newborn rhesus macaques inoculated with
       the nonpathogenic molecular clone, SIVmac1A11, had transient, low-level
       viremia, seroconverted by 10 weeks after inoculation, had normal weight
       gain, and remained healthy for over 1 year. These results indicate that
       (i) newborn rhesus macaques infected with an uncloned, virulent SIVmac
       isolate have a more rapid, fulminant disease course than do adults
       inoculated with the same virus, (ii) the most rapid disease progression
       is associated with lack of a detectable humoral immune response in
       SIV-infected infant macaques, (iii) a molecularly cloned, attenuated SIV
       isolate is nonpathogenic in neonatal macaques, and (iv) SIV-infected
       neonatal macaques exhibit patterns of infection, virus load, and disease
       progression similar to those observed in human immunodeficiency
       virus-infected children. This SIV/neonatal rhesus model of pediatric
       AIDS provides a rapid, sensitive model with which to compare the
       virulence of SIV isolates and to study the mechanisms underlying the
       differences in disease progression in human immunodeficiency
       virus-infected infants.
 DE    Animal  Animals, Newborn  Disease Models, Animal  Macaca mulatta  Simian
       Acquired Immunodeficiency Syndrome/*ETIOLOGY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  SIV/*PATHOGENICITY  Virulence  JOURNAL
       ARTICLE

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

