       Document 0622
 DOCN  M9630622
 TI    Lymphocyte-tropic simian immunodeficiency virus causes persistent
       infection in the brains of rhesus monkeys.
 DT    9603
 AU    Stephens EB; Liu ZQ; Zhu GW; Adany I; Joag SV; Foresman L; Berman NE;
       Narayan O; Department of Microbiology, Molecular Genetics and
       Immunology,; Marion Merrell Dow Laboratory for Viral Pathogenesis,
       University; of Kansas Medical Center, Kansas City 66160-7240, USA.
 SO    Virology. 1995 Nov 10;213(2):600-14. Unique Identifier : AIDSLINE
       MED/96074535
 AB    Molecularly cloned SIVmac239 is the prototypical SIVmac
       lymphocyte-tropic virus that replicates productively in lymphocytes but
       poorly in macrophages. In macaques, the virus causes activation and
       productive infection of T lymphocytes which invade the central nervous
       system (CNS) early after infection in the animal. However, infected
       animals develop immunosuppression and AIDS but rarely overt neurological
       disease. In this study, we examined multiple regions of the brain and
       spinal cord for the presence of SIV env sequences and histological
       lesions in five macaques that had been infected with SIVmac239 for 1.7
       to 2.25 years. Histopathological examination of the brain revealed no
       lesions consistent with encephalitis; however, viral DNA was found in
       all five brains. In one animal the virus caused infection in a widely
       disseminated pattern from the frontal cortex to the distal end of the
       spinal cord, whereas in the other four animals infection in the CNS
       occurred in a nonspecific, focal pattern. Sequence analyses were
       performed on gp120 sequences isolated from selected regions of the CNS
       and compared to gp120 sequences isolated from corresponding lymph nodes,
       a tissue known to support productive replication of SIVmac239.
       Examination of the viral sequences from the CNS tissue from two animals
       (macaques 10F and 14F) revealed a low mutation rate when compared to the
       sequences isolated from the lymph node tissues. The percentage change in
       the amino acid sequence was approximately 1% for CNS clones versus > or
       = 3% for clones isolated from the lymph node. The majority of the CNS
       viral sequences of macaques 10F and 14F had none of the genetic markers
       shown in a previous study to be associated with macrophage-tropic
       variants and indeed retained a nucleotide sequence of similar to the
       original lymphocyte-tropic virus used for inoculation despite almost 2
       years of persistent infection in the animals. Construction of chimeric
       viruses with V1-V5 regions of selected macaque 10F and macaque 14F
       CNS-gp120 clones confirmed the predicted lymphocyte-tropic nature of
       these env genes. In contrast, the gp120 sequences isolated from the CNS
       tissue of one of the other three animals (macaque 13F) had a mutation
       rate comparable to that observed for the lymph node clones. The CNS
       clones from this animal had amino acid substitutions that were
       previously shown to be associated with macrophage tropism. Compared to
       the chimeric viruses constructed with V1-V5 sequences from macaques 10F
       and 14F, viruses constructed with the V1-V5 sequences of several macaque
       13F brain clones did not yield infectious virus.(ABSTRACT TRUNCATED AT
       400 WORDS)
 DE    Amino Acid Sequence  Amino Acids/ANALYSIS  Animal  Base Sequence
       Brain/*VIROLOGY  Cell Line  Cloning, Molecular  CD4-Positive
       T-Lymphocytes/VIROLOGY  DNA Primers  Gene Products, gag/ANALYSIS
       Genome, Viral  Human  HIV Envelope Protein gp120/ANALYSIS/CHEMISTRY
       Lymph Nodes/PATHOLOGY/VIROLOGY  Lymphocytes/*VIROLOGY  Macaca mulatta
       Macrophages/VIROLOGY  Molecular Sequence Data  Simian Acquired
       Immunodeficiency Syndrome/PATHOLOGY/*VIROLOGY  Spinal Cord/VIROLOGY
       Support, U.S. Gov't, P.H.S.  SIV/GENETICS/*PHYSIOLOGY  Virus Latency
       Virus Replication  JOURNAL ARTICLE

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

