Natural isolates of simian virus 40 from immunocompromised monkeys display extensive genetic heterogeneity: new implications for polyomavirus disease.
Simian virus 40 (SV40) DNAs in brain tissue and peripheral blood mononuclear cells (PBMCs) of eight simian immunodeficiency virus-infected rhesus monkeys with SV40 brain disease were analyzed. We report the detection, cloning, and identification of five new SV40 strains following a quadruple testing-verification strategy. SV40 genomes with archetypal regulatory regions (containing a duplication within the G/C-rich regulatory region segment and a single 72-bp enhancer element) were recovered from seven animal brains, two tissues of which also contained viral genomes with nonarchetypal regulatory regions (containing a duplication within the G/C-rich regulatory region segment as well as a variable duplication within the enhancer region). In contrast, PBMC DNAs from five of six animals had viral genomes with both regulatory region types. It appeared, based on T-antigen variable-region sequences, that nonarchetypal virus variants arose de novo within each animal. The eighth animal exclusively yielded a new type of SV40 strain (SV40-K661), containing a protoarchetypal regulatory region (lacking a duplication within the G/C-rich segment of the regulatory region and containing one 72-bp element in the enhancer region), from both brain tissue and PBMCs. The presence of SV40 in PBMCs suggests that hematogenous spread of viral infection may occur. An archetypal version of a virus similar to SV40 reference strain 776 (a kidney isolate) was recovered from one brain, substantiating the idea that SV40 is neurotropic as well as kidney-tropic. Indirect evidence suggests that maternal-infant transmission of SV40 may have occurred in one animal. These findings provide new insights for human polyomavirus disease.
Lednicky
J A
JA
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
Arrington
A S
AS
Stewart
A R
AR
Dai
X M
XM
Wong
C
C
Jafar
S
S
Murphey-Corb
M
M
Butel
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology / Q000821:virology; D002213:Capsid / Q000235:genetics; D036022:Capsid Proteins; D046508:Culture Techniques; D004279:DNA, Viral; D018740:Genetic Heterogeneity; D014644:Genetic Variation; D016867:Immunocompromised Host; D007962:Leukocytes / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D027601:Polyomavirus Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary* / Q000821:virology*; D012689:Sequence Homology, Nucleic Acid; D013539:Simian virus 40 / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary* / Q000821:virology*
D036022:Capsid Proteins; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus