| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 151, 793-803, Copyright © 1997 by American Society for Investigative Pathology
REGULAR ARTICLES |
MC Zink, AM Amedee, JL Mankowski, L Craig, P Didier, DL Carter, A Munoz, M Murphey-Corb and JE Clements
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
To investigate the viral and host factors that contribute to neurological disease, nine macaques were intravenously co-inoculated with SIV/DeltaB670, a primary isolate of SIV consisting of at least 21 different genotypes, and SIV/17E-Fr, a neurovirulent recombinant clone. CD4+ cell counts and antigenemia were measured throughout infection. The SIV env V1 region was amplified from brain and peripheral blood mononuclear cell DNA to compare the genotypes present in brain and blood. Seven of the 9 macaques (78%) developed typical SIV-associated neurological lesions classified as severe (4 macaques), moderate (2 macaques), or mild (1 macaque) with a mean time to euthanasia of 7 months. Macaques with severe neurological lesions progressed more rapidly, with a mean time to euthanasia of 3-6 months. SIV/17E-Fr was detected in brain homogenates from all four macaques with severe encephalitis, and in three of the four, SIV/17E-Fr was the only genotype identified in the central nervous system. Macaques with less severe or no neurological lesions usually had one of various genotypes of SIV/DeltaB670 in brain. A variety of genotypes of SIV/DeltaB670 and SIV/17E-Fr were detected in peripheral blood mononuclear cells throughout infection. Macaques with severe neurological lesions had the most precipitous declines in CD4+ cell counts, the highest levels of antigenemia, and the greatest expression of viral RNA and protein in the central nervous system. Macaca nemestrina were more likely to develop severe neurological lesions than M. mulatta or M. fascicularis (P = 0.048). This study demonstrated that neurovirulent strains within the virus swarm can selectively enter and become established in the central nervous system and that the neurological lesions that develop are correlated with the development of host immunosuppression. The species differences in severity of neurological lesions seen in this study suggest that host factors are also important in determining the outcome of lentiviral infection.
This article has been cited by other articles:
 |
|
 |
|
  S. J. Bissel, G. Wang, D. Bonneh-Barkay, A. Starkey, A. M. Trichel, M. Murphey-Corb, and C. A. Wiley Systemic and Brain Macrophage Infections in Relation to the Development of Simian Immunodeficiency Virus Encephalitis J. Virol., May 15, 2008; 82(10): 5031 - 5042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Chase, A. R. Sedaghat, J. R. German, L. Gama, M. C. Zink, J. E. Clements, and R. F. Siliciano Severe Depletion of CD4+ CD25+ Regulatory T Cells from the Intestinal Lamina Propria but Not Peripheral Blood or Lymph Nodes during Acute Simian Immunodeficiency Virus Infection J. Virol., December 1, 2007; 81(23): 12748 - 12757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Dudaronek, S. A. Barber, and J. E. Clements CUGBP1 Is Required for IFNbeta-Mediated Induction of Dominant-Negative CEBPbeta and Suppression of SIV Replication in Macrophages J. Immunol., December 1, 2007; 179(11): 7262 - 7269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Brown, M. Czapiga, J. Kabat, Q. Dang, I. Ourmanov, Y. Nishimura, M. A. Martin, and V. M. Hirsch Unique Pathology in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques Is Consistent with a Pathogenesis Distinct from That of Classical AIDS J. Virol., June 1, 2007; 81(11): 5594 - 5606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Bissel, G. Wang, A. M. Trichel, M. Murphey-Corb, and C. A. Wiley Longitudinal Analysis of Monocyte/Macrophage Infection in Simian Immunodeficiency Virus-Infected, CD8+ T-Cell-Depleted Macaques that Develop Lentiviral Encephalitis Am. J. Pathol., May 1, 2006; 168(5): 1553 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Overholser, T. Babas, M. C. Zink, S. A. Barber, and J. E. Clements CD4-Independent Entry and Replication of Simian Immunodeficiency Virus in Primary Rhesus Macaque Astrocytes Are Regulated by the Transmembrane Protein J. Virol., April 15, 2005; 79(8): 4944 - 4951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Poluektova, S. Gorantla, J. Faraci, K. Birusingh, H. Dou, and H. E. Gendelman Neuroregulatory Events Follow Adaptive Immune-Mediated Elimination of HIV-1-Infected Macrophages: Studies in a Murine Model of Viral Encephalitis J. Immunol., June 15, 2004; 172(12): 7610 - 7617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. O'Neil, C. Suwyn, D. C. Anderson, G. Niedziela, J. Bradley, F. J. Novembre, J. G. Herndon, and H. M. McClure Correlation of Acute Humoral Response with Brain Virus Burden and Survival Time in Pig-Tailed Macaques Infected with the Neurovirulent Simian Immunodeficiency Virus SIVsmmFGb Am. J. Pathol., April 1, 2004; 164(4): 1157 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Barber, J. L. Uhrlaub, J. B. DeWitt, P. M. Tarwater, and M. C. Zink Dysregulation of Mitogen-Activated Protein Kinase Signaling Pathways in Simian Immunodeficiency Virus Encephalitis Am. J. Pathol., February 1, 2004; 164(2): 355 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Dehghani, B. A. Puffer, R. W. Doms, and V. M. Hirsch Unique Pattern of Convergent Envelope Evolution in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques: Association with CD4-Independent Usage of CCR5 J. Virol., June 1, 2003; 77(11): 6405 - 6418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Babas, D. Munoz, J. L. Mankowski, P. M. Tarwater, J. E. Clements, and M. C. Zink Role of Microglial Cells in Selective Replication of Simian Immunodeficiency Virus Genotypes in the Brain J. Virol., December 6, 2002; 77(1): 208 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Patrick, J. B. Johnston, and C. Power Lentiviral Neuropathogenesis: Comparative Neuroinvasion, Neurotropism, Neurovirulence, and Host Neurosusceptibility J. Virol., July 17, 2002; 76(16): 7923 - 7931. [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Jordan-Sciutto, G. Wang, M. Murphey-Corb, and C. A. Wiley Cell Cycle Proteins Exhibit Altered Expression Patterns in Lentiviral-Associated Encephalitis J. Neurosci., March 15, 2002; 22(6): 2185 - 2195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Bissel, G. Wang, M. Ghosh, T. A. Reinhart, S. Capuano III, K. Stefano Cole, M. Murphey-Corb, M. Piatak Jr., J. D. Lifson, and C. A. Wiley Macrophages Relate Presynaptic and Postsynaptic Damage in Simian Immunodeficiency Virus Encephalitis Am. J. Pathol., March 1, 2002; 160(3): 927 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Broussard, S. I. Staprans, R. White, E. M. Whitehead, M. B. Feinberg, and J. S. Allan Simian Immunodeficiency Virus Replicates to High Levels in Naturally Infected African Green Monkeys without Inducing Immunologic or Neurologic Disease J. Virol., March 1, 2001; 75(5): 2262 - 2275. [Abstract] [Full Text]
|
|
|
|
|
|
K. L. Jordan-Sciutto, G. Wang, M. Murphy-Corb, and C. A. Wiley Induction of Cell-Cycle Regulators in Simian Immunodeficiency Virus Encephalitis Am. J. Pathol., August 1, 2000; 157(2): 497 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Zink, K. Suryanarayana, J. L. Mankowski, A. Shen, M. Piatak Jr., J. P. Spelman, D. L. Carter, R. J. Adams, J. D. Lifson, and J. E. Clements High Viral Load in the Cerebrospinal Fluid and Brain Correlates with Severity of Simian Immunodeficiency Virus Encephalitis J. Virol., December 1, 1999; 73(12): 10480 - 10488. [Abstract] [Full Text]
|
|
|
|
|
|
D. C. Adamson, K. L. Kopnisky, T. M. Dawson, and V. L. Dawson Mechanisms and Structural Determinants of HIV-1 Coat Protein, gp41-Induced Neurotoxicity J. Neurosci., January 1, 1999; 19(1): 64 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sopper, U. Sauer, S. Hemm, M. Demuth, J. Muller, C. Stahl-Hennig, G. Hunsmann, V. ter Meulen, and R. Dorries Protective Role of the Virus-Specific Immune Response for Development of Severe Neurologic Signs in Simian Immunodeficiency Virus-Infected Macaques J. Virol., December 1, 1998; 72(12): 9940 - 9947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Mankowski, D. L. Carter, J. P. Spelman, M. L. Nealen, K. R. Maughan, L. M. Kirstein, P. J. Didier, R. J. Adams, M. Murphey-Corb, and M. C. Zink Pathogenesis of Simian Immunodeficiency Virus Pneumonia : An Immunopathological Response to Virus Am. J. Pathol., October 1, 1998; 153(4): 1123 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Edinger, J. L. Mankowski, B. J. Doranz, B. J. Margulies, B. Lee, J. Rucker, M. Sharron, T. L. Hoffman, J. F. Berson, M. C. Zink, et al. CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain PNAS, December 23, 1997; 94(26): 14742 - 14747. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
