LYMPHOCYTE-TROPIC SIMIAN IMMUNODEFICIENCY VIRUS CAUSES PERSISTENT INFECTION IN THE BRAINS OF RHESUS-MONKEYS

被引:25
作者
STEPHENS, EB [1 ]
LIU, ZQ [1 ]
ZHU, GW [1 ]
ADANY, I [1 ]
JOAG, SV [1 ]
FORESMAN, L [1 ]
BERMAN, NEJ [1 ]
NARAYAN, O [1 ]
机构
[1] UNIV KANSAS, MED CTR, DEPT ANAT & CELL BIOL, KANSAS CITY, KS 66160 USA
关键词
D O I
10.1006/viro.1995.0032
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Molecularly cloned SIV(mac)239 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 SIV(mac)239 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 SIV(mac)239. 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 greater than or equal to 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. These data suggest that following entry into the CSF early during infection in the animals, SIV(mac)239 caused infection in the CNS. In some animals, the Viral env sequences recovered by the PCR suggested that minimal replication had occurred, whereas in another macaque virus replication had progressed with gradual selection of a more macrophage-tropic genotype. (C) 1995 Academic Press, Inc.
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页码:600 / 614
页数:15
相关论文
共 47 条
[1]   ANALYSIS OF ENVELOPE CHANGES ACQUIRED BY SIV(MAC)239 DURING NEUROADAPTATION IN RHESUS MACAQUES [J].
ANDERSON, MG ;
HAUER, D ;
SHARMA, DP ;
JOAG, SV ;
NARAYAN, O ;
ZINK, MC ;
CLEMENTS, JE .
VIROLOGY, 1993, 195 (02) :616-626
[2]  
ANDERSON V M, 1988, Pediatric Pathology, V8, P417
[3]   RENAL COMPLICATIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 [J].
BOURGOIGNIE, JJ .
KIDNEY INTERNATIONAL, 1990, 37 (06) :1571-1584
[4]  
COHEN AH, 1988, MODERN PATHOL, V1, P87
[5]  
DESROSIERS RC, 1991, AM J PATHOL, V139, P29
[6]   HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF THE NERVOUS-SYSTEM - PATHOGENETIC MECHANISMS [J].
EPSTEIN, LG ;
GENDELMAN, HE .
ANNALS OF NEUROLOGY, 1993, 33 (05) :429-436
[7]   A TECHNIQUE FOR RADIOLABELING DNA RESTRICTION ENDONUCLEASE FRAGMENTS TO HIGH SPECIFIC ACTIVITY [J].
FEINBERG, AP ;
VOGELSTEIN, B .
ANALYTICAL BIOCHEMISTRY, 1983, 132 (01) :6-13
[8]   EARLY ACTIVATION OF PBMC AND APPEARANCE OF ANTIVIRAL CD8+ CELLS INFLUENCE THE PROGNOSIS OF SIV-INDUCED DISEASE IN RHESUS MACAQUES [J].
JOAG, SV ;
ADAMS, RJ ;
FORESMAN, L ;
GALBREATH, D ;
ZINK, MC ;
PINSON, DM ;
MCCLURE, H ;
NARAYAN, O .
JOURNAL OF MEDICAL PRIMATOLOGY, 1994, 23 (2-3) :108-116
[9]   PATHOGENESIS OF SIVMAC INFECTION IN CHINESE AND INDIAN RHESUS MACAQUES - EFFECTS OF SPLENECTOMY ON VIRUS BURDEN [J].
JOAG, SV ;
STEPHENS, EB ;
ADAMS, RJ ;
FORESMAN, L ;
NARAYAN, O .
VIROLOGY, 1994, 200 (02) :436-446
[10]   SIMIAN IMMUNODEFICIENCY VIRUS SIVMAC CHIMERIC VIRUS WHOSE ENV GENE WAS DERIVED FROM SIV-ENCEPHALITIC BRAIN IS MACROPHAGE-TROPIC BUT NOT NEUROVIRULENT [J].
JOAG, SV ;
STEPHENS, EB ;
GALBREATH, D ;
ZHU, GW ;
LI, Z ;
FORESMAN, L ;
ZHAO, LJ ;
PINSON, DM ;
NARAYAN, O .
JOURNAL OF VIROLOGY, 1995, 69 (02) :1367-1369