Abstract
The central nervous system (CNS) impairment is a consequence seen in SIV infection of rhesus macaques of Indian-origin, which is more common in infected macaques with rapid disease progression than in those with conventional disease progression. Here, we investigated the CNS damages in SIVmac239-infected Chinese rhesus macaques. We demonstrated that SIV infection of Chinese macaques could cause neuropathological impairments, which was evidenced by appearance of SIV-RNA positive cells, the infiltration of activated macrophages and abundant multinucleated giant cells (MNGCs) in the different regions of the brains. The animals with high viremia and short survival time (average of 16 weeks, rapid progression, RP) had severer neuropathological changes than those with conventional progression (CP). As compared with the RP animals, CP macaques had lower viremia and much longer survival time (average of 154 weeks). These findings indicate that SIVmac239 infection of Chinese rhesus macaque can be used as a suitable animal model and alternative resource for nueroAIDS research.
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References
Barber SA, Gama L, Dudaronek JM et al (2006) Mechanism for the establishment of transcriptional HIV latency in the brain in a simian immunodeficiency virus-macaque model. J Infectious Diseases 193:963–970
Baskin G, Murphey-Corb M, Martin L et al (1991) Lentivirus-induced pulmonary lesions in rhesus monkeys (Macaca mulatta) infected with simian immunodeficiency virus. Veterinary Pathol Online 28:506–513
Brown CR, Czapiga M, Kabat J et al (2007) Unique pathology in simian immunodeficiency virus-infected rapid progressor macaques is consistent with a pathogenesis distinct from that of classical AIDS. J Virol 81:5594–5606
Budka H (1991) Neuropathology of human immunodeficiency virus infection. Brain Pathol 1:163–175
Chakrabarti L, Hurtrel M, Maire MA et al (1991) Early viral replication in the brain of SIV-infected rhesus monkeys. Am J Pathol 139:1273–1280
Champoux M, Higley JD, Suomi SJ et al (1997) Behavioral and physiological characteristics of Indian and Chinese-Indian hybrid rhesus macaque infants. Dev Psychobiol 31:49–63
Clarke MR, O'Neil JAS (1999) Morphometric comparison of Chinese–origin and Indian–derived rhesus monkeys (Macaca mulatta). Am J Primatol 47:335–346
Clifford DB, Ances BM (2013) HIV-associated neurocognitive disorder. Lancet Infect Dis 13:976–986
Doxiadis GG, Otting N, de Groot NG et al (2003) Evolutionary stability of MHC class II haplotypes in diverse rhesus macaque populations. Immunogenetics 55:540–551
Forbi J, Agwale S (2009) Inverted CD4+/CD8+ ratio associated with AIDS event and death in HIV-1 infected individuals in Nasarawa State, Nigeria. Tanzania journal of health research 11(3).
Gonzalez RG, Cheng LL, Westmoreland SV et al (2000) Early brain injury in the SIV-macaque model of AIDS. AIDS 14:2841–2849
Harbison C, Zhuang K, Gettie A et al (2014) Giant cell encephalitis and microglial infection with mucosally transmitted simian-human immunodeficiency virus SHIVSF162P3N in rhesus macaques. J Neurovirology 20:62–72
Heaton R, Clifford D, Franklin D et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy CHARTER Study. Neurology 75:2087–2096
Horn TF, Huitron-Resendiz S, Weed MR et al (1998) Early physiological abnormalities after simian immunodeficiency virus infection. Proc Natl Acad Sci U S A 95:15072–15077
Lackner AA, Smith MO, Munn RJ et al (1991) Localization of simian immunodeficiency virus in the central nervous system of rhesus monkeys. Am J Pathol 139:609–621
Liner KJ II, Hall CD, Robertson KR et al (2008) Effects of antiretroviral therapy on cognitive impairment. Current HIV/AIDS Reports 5:64–71
Ling B, Veazey RS, Luckay A et al (2002) SIVmac pathogenesis in rhesus macaques of Chinese and Indian origin compared with primary HIV infections in humans. Aids 16:1489–1496
Marcondes MCG, Flynn C, Watry DD, Zandonatti M, Fox HS (2010) Methamphetamine increases brain viral load and activates natural killer cells in simian immunodeficiency virus-infected monkeys. Am J Pathol 177:355–361
Marthas ML, Lu D, Penedo MC et al (2001) Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses. AIDS Res Hum Retroviruses 17:1455–1466
Maschke M, Kastrup O, Esser S et al (2000) Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). J Neurol Neurosurg Psychiatry 69:376–380
Matsuda K, Brown CR, Foley B et al (2013) Laser capture microdissection assessment of virus compartmentalization in the central nervous systems of macaques infected with neurovirulent simian immunodeficiency virus. J Virol 87:8896–8908
McArthur JC, Haughey N, Gartner S et al (2003) Human immunodeficiency virus-associated dementia: an evolving disease. J Neurovirol 9:205–221
McArthur JC, Steiner J, Sacktor N et al (2010) Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol 67:699–714
Mellors JW, Rinaldo CR, Gupta P et al (1996) Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272:1167–1170
Nowlin BT, Burdo TH, Midkiff CC et al (2015) SIV encephalitis lesions are composed of CD163+ macrophages present in the central nervous system during early SIV infection and SIV-positive macrophages recruited terminally with AIDS. Am J Pathol 185:1649–1665
O'Neil SP, Suwyn C, Anderson DC et al (2004) 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 164:1157–1172
Orandle MS, Williams KC, MacLean AG et al (2001) Macaques with rapid disease progression and simian immunodeficiency virus encephalitis have a unique cytokine profile in peripheral lymphoid tissues. J Virol 75:4448–4452
Otting N, de Vos-Rouweler AJ, Heijmans CM et al (2007) MHC class I A region diversity and polymorphism in macaque species. Immunogenetics 59:367–375
Penedo MC, Bontrop RE, Heijmans CM et al (2005) Microsatellite typing of the rhesus macaque MHC region. Immunogenetics 57:198–209
Reimann KA, Parker RA, Seaman MS et al (2005) Pathogenicity of simian-human immunodeficiency virus SHIV-89.6 P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses. J Virol 79:8878–8885
Sacktor N, McDermott MP, Marder K et al (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8:136–142
Sharma DP, Zink MC, Anderson M et al (1992) Derivation of neurotropic simian immunodeficiency virus from exclusively lymphocytetropic parental virus: pathogenesis of infection in macaques. J Virol 66:3550–3556
Simpson DM, Kitch D, Evans SR et al (2006) HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology 66:1679–1687
Smyth K, Affandi JS, McArthur JC et al (2007) Prevalence of and risk factors for HIV-associated neuropathy in Melbourne, Australia 1993–2006. HIV Med 8:367–373
Viray J, Rolfs B, Smith DG et al (2001) Comparison of the frequencies of major histocompatibility (MHC) class-II DQA1 and DQB1 alleles in Indian and Chinese rhesus macaques (Macaca mulatta). Comp Med 51:555–561
Westmoreland SV, Halpern E, Lackner AA et al (1998) Simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression. J Neurovirol 4:260–268
Williams R, Bokhari S, Silverstein P et al (2008) Nonhuman primate models of NeuroAIDS. J Neurovirol 14:292–300
Xiao Q, Li J, Yu Q et al (2015) Distinct compartmentalization in the CNS of SHIVKU-1-infected Chinese rhesus macaque is associated with severe neuropathology. J Acquir Immune Defic Syndr 70:e168–e171
Zhuang K, Leda AR, Tsai L et al (2014) Emergence of CD4 independence envelopes and astrocyte infection in R5 simian-human immunodeficiency virus model of encephalitis. J Virol 88:8407–8420
Acknowledgments
We are grateful to Dr. Vanessa M Hirsch for the SIVmac239 ISH probes templates and Dr. Kenta Matsuda for the technique support of ISH. This work was supported by the National Natural Science Foundation of China (81471943 to K.Z.; 81301428 to L.Z.; 81271334 to W.Z.H. and 81201261 to J.Z.) and by the Fundamental Research Funds for the Central Universities (2042016kf0186 to K.Z. and 2042015kf0188 to L.Z.).
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Hang Liu and Qian-Hao Xiao contributed equally to this work.
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Liu, H., Xiao, QH., Liu, JB. et al. SIV Infection Impairs the Central Nervous System in Chinese Rhesus Macaques. J Neuroimmune Pharmacol 11, 592–600 (2016). https://doi.org/10.1007/s11481-016-9682-9
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DOI: https://doi.org/10.1007/s11481-016-9682-9