Host genetic factors predisposing to HIV-associated neurocognitive disorder

Current HIV/AIDS Reports

Volumn 11, Issue 3, 2014, Pages 336-352

  Kallianpur, Asha R ^a,b   Levine, Andrew J ^c  

^a LERNER RESEARCH INSTITUTE   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Central nervous system; CNS; Combination antiretroviral therapy (cART); HAND; HIV; HIV associated neurocognitive disorders

Indexed keywords

DOPAMINE; MITOCHONDRIAL DNA; RNA;

BRAIN REGION; COMORBIDITY; DEGENERATIVE DISEASE; DNA DAMAGE; DRUG METABOLISM; EPIGENETICS; GENETIC ASSOCIATION; GENETIC DIFFERENCE; GENETIC MARKER; GENETIC PREDISPOSITION; HEREDITY; HIV ASSOCIATED DEGENERATIVE DISEASE; HIV ASSOCIATED DEMENTIA; HOST SUSCEPTIBILITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNOREGULATION; INFECTION RISK; INFLAMMATION; LONGITUDINAL STUDY; MACHINE LEARNING; NEUROPATHOLOGY; PHENOTYPE; QUALITY OF LIFE; REVIEW; SYSTEMS BIOLOGY; TRANSCRIPTOMICS; AIDS DEMENTIA COMPLEX; COMPLICATION; GENETICS; GENOMICS;

AIDS DEMENTIA COMPLEX; GENETIC PREDISPOSITION TO DISEASE; GENOMICS; HIV INFECTIONS; HUMANS;

EID: 84925548486     PISSN: 15483568     EISSN: 15483576     Source Type: Journal    
DOI: 10.1007/s11904-014-0222-z     Document Type: Review

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103. • Yuferov V, Ho A, Morgello S, Yang Y, Ott J, Kreek MJ. Expression of ephrin receptors and ligands in postmortem brains of HIV-infected subjects with and without cognitive impairment. J Neuroimmune Pharmacol. 2013;8:333-44. These authors examined expression of ephrin (EPH) genes important in synapse formation and glutamine metabolism in relation to HIV serostatus, immune function, and premortem neurocognitive function using brain tissues from the Manhattan HIV Brain Bank.
104. Eletto D, Russo G, Passiatore G, et al. Inhibition of SNAP25 expression by HIV-1 Tat involves the activity of mir-128a. J Cell Physiol. 2008;216:764-70.
105. • Mukerjee R, Chang JR, Del Valle L, et al. Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders. J Biol Chem. 2011;286:34976-85. This study, which documented expression of Vpr in brain tissues from patients with HIV encephalitis, used primary neuronal cultures or cell lines and microRNA and gene-expression assays to link viral protein R (Vpr) exposure to dysregulation of multiple cellular pathways and their target genes that likely play significant roles in HAND.
106. Yelamanchili SV, Chaudhuri AD, Chen LN, Xiong H, Fox HS 2010 MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease. Cell Death Dis. 1:e77
107. Noorbakhsh F, Ramachandran R, Barsby N, et al. MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival. FASEB J. 2010;24:1799-812.
108. Liu J, Sisk JM, Gama L, Clements JE,Witwer KW. Tristetraprolin expression and microRNA-mediated regulation during simian immunodeficiency virus infection of the central nervous system. Mol Brain. 2013;6:40.
109. • Chaudhuri AD, Yelamanchili SV, Fox HS. MicroRNA-142 reduces monoamine oxidase A expression and activity in neuronal cells by downregulating SIRT1. PLoS One. 2013;8:e79579. These authors investigated downstream effects of miR-142 upregulation in neurons in vitro, which is observed in HAND, revealing its possible contribution to dopaminergic dysfunction in HAND.
110. • Sisk JM,Witwer KW, Tarwater PM, Clements JE. SIV replication is directly downregulated by four antiviral miRNAs. Retrovirology. 2013;10:95. An epigenetic study that demonstrated the role of host microRNAs in regulating replication of SIV in macrophage-lineage cells in vitro, suggesting a potential therapeutic strategy.
111. • Zhou L, Pupo GM, Gupta P, et al. A parallel genome-wide mRNA and microRNA profiling of the frontal cortex of HIV patients with and without HIV-associated dementia shows the role of axon guidance and downstream pathways in HIV-mediated neurodegeneration. BMC Genomics. 2012;13:677. Another comprehensive review of HAND which discusses numerous mechanisms of neuropathogenesis of HIV-1 proteins, the impact of reservoirs, and the application of microarray technologies to the study of HIV-associated dementia.
112. • Atluri VS, Kanthikeel SP, Reddy PV, Yndart A, Nair MP. Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND). PLoS One. 2013;8:e61399. This study investigated the differential expression of genes involved in synaptic plasticity in clade B- and clade C-infected primary human astrocytes by microarray analysis; down-regulation of these genes, with decreased dendritic spine density and induction of apoptosis were reported, with important differences noted by clade of virus.
113. • Lucas CH, Calvez M, Babu R, Brown A. Altered subcellular localization of the NeuN/Rbfox3 RNA splicing factor in HIV-associated neurocognitive disorders (HAND). Neurosci Lett. 2014;558:97-102. This neuropathological study identified distinctly abnormal nuclear localization of a previously uncharacterized RNA splicing factor in HIV+individuals with HAND as compared to those without HAND.
114. • Saiyed ZM, Gandhi N, Agudelo M, et al. HIV-1 Tat upregulates expression of histone deacetylase-2 (HDAC2) in human neurons: implication for HIV-associated neurocognitive disorder (HAND). Neurochem Int. 2011;58:656 - 64. The first study to examine histone deacetylation in the context of HAND neuropathogenesis, which showed that HIV Tat protein dysregulates HDAC2 expression in neuronal cells, with downstream effects on synaptic plasticity and genes involved in neuronal function such as CREB.
115. Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov. 2008;7:854-68.
116. Wiech NL, Fisher JF, Helquist P, Wiest O. Inhibition of histone deacetylases: a pharmacological approach to the treatment of non-cancer disorders. Curr Top Med Chem. 2009;9:257- 71.
117. • Desplats P, Dumaop W, Smith D, et al. Molecular and pathologic insights from latent HIV-1 infection in the human brain. Neurology. 2013;80:1415-23. A case-control study of epigenetic markers in relation to HIV latency, neurocognitive function, clinical and neuropathologic features, which revealed increased expression of "silencing" chromatin modifiers in latent cases; latent cases also had more cognitive impairment than HIV+controls with undetectable HIV DNA, RNA or p24 protein in brain.
118. • Narasipura SD, Kim S, Al-Harthi L. Epigenetic regulation of HIV-1 latency in astrocytes. J Virol. 2014;88:3031 - 8. This study showed that class I histone deacetylases (HDACs) and a lysine-specific histone methyltransferase play a significant role in silencing HIV transcription in astrocytes and supports the role of astrocytes as virus reservoirs.
119. • Hakre S, Chavez L, Shirakawa K, Verdin E. Epigenetic regulation of HIV latency. Curr Opin HIVAIDS. 2011;6:19-24. This article reviews how histone modifications and chromatin remodeling affect transcriptional activity of the HIV promoter in the context of HIV latency.
120. • Abdel-Hameed EA, Ji H, Sherman KE, Shata MT. Epigenetic modification of FOXP3 in patients with chronic HIV infection. J Acquir Immune Defic Syndr. 2014;65:19-26. This study presents evidence suggesting that altered methylation of FOXP3 predisposes to higher T(reg) frequency in gut mucosa of HIV-infected patients, which impacts chronic immune activation, one of several factors involved in HAND.
121. Ghosh SK, McCormick TS, Eapen BL, Yohannes E, Chance MR, Weinberg A. Comparison of epigenetic profiles of human oral epithelial cells from HIV-positive (on HAART) and HIV-negative subjects. Epigenetics. 2013;8:703-9.
122. • Regan PM, Dave RS, Datta PK, Khalili K. Epigenetics of microopioid receptors: intersection with HIV-1 infection of the central nervous system. J Cell Physiol. 2012;227:2832-41. Review of what is known about epigenetic regulation of ì-opioid receptor (MOR) expression, (epigenetic and transcriptional regulation as well as alternative splicing), which discusses how differential regulation of newly identified MOR isoforms by opioids and HIV-1 may impact HAND.
123. Hulgan T SD, BushW, Ellis R, Letendre S, Straub P, Murdock D, Franklin D, Grant I, and Kallianpur A for the CHARTER Group.: Mitochondrial DNA haplogroups and neurocognitive impairment in the CHARTER Cohort. Abstract#465, 21st Conference on Retroviruses and Opportunistic Infections; March 5-8, Boston, MA, USA, 2014.
124. Kallianpur AR CJ, Coe CC, Gelman BB: Brain iron transport is associated with neurocognitive performance in HIV/AIDS. Abstract#458, 21st Conference on Retroviruses and Opportunistic Infections; March 5-8, Boston, MA, USA, 2014.
125. • Pitcher J, Abt A, Myers J, et al. Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction. J Clin Invest. 2014;124:656-69. This study makes potentially important links between iron metabolism in the brain, regulation of chemokines involved in neuronal function, and opiate-induced dendritic injury in humans with HAND and confirmed these findings in the non-human primate model of neuroAIDS.
126. Gill AJ, Ambegaokar SS, Kovacsics CE, Cross SA, Gelman BB, Kolson DL. Heme oxygenase-1 polymorphisms and protein deficiency associated with neurological disease in HIV, 21st Conference on Retroviruses and Opportunistic Infections; March 5-8. Boston: MA, USA; 2014.
127. • Holzinger ER, Hulgan T, Ellis RJ, et al. Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER. J Neurovirol. 2012;18:511-20. This mitochondrial genome-wide study supports the concept that mitochondrial DNA variants can modulate HIV neuropathogenesis, although peripheral neuropathy, not HAND, was studied.
128. Kallianpur AR, Hulgan T, Canter JA, et al. Hemochromatosis (HFE) gene mutations and peripheral neuropathy during antiretroviral therapy. AIDS. 2006;20:1503-13. (Pubitemid 44100211)
129. • Granziera C, Daducci A, Simioni S, et al. Micro-structural brain alterations in aviremic HIV+ patients with minor neurocognitive disorders: a multi-contrast study at high field. PLoS One. 2013;8: e72547. This study, involvingHIV+ subjects with and without mild neurocognitive disorder (MND) whose viral load was undetectable, showed micro-structural brain tissue alterations in MND+patients on effective cART and suggested the value of multicontrast, high-field MRI in discriminating between HIV+ patients on cART with and without mild HAND.
130. Morales D, Acevedo SF, Skolasky RL, et al. Translational spatial task and its relationship to HIV-associated neurocognitive disorders and apolipoprotein E in HIV-seropositive women. J Neurovirol. 2012;18:488-502.
131. • Steinbrink F, Evers S, Buerke B, et al. Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration. Eur J Neurol. 2013;20:420-8. This MRI and CSF study in 94 HIV-infected patients without opportunistic infections confirmed correlations between patterns of brain damage, CSF levels of total tau protein, and HAND as distinct from Alzheimer's disease.
132. Everall I, Vaida F, Khanlou N, et al. Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy. J Neurovirol. 2009;15:360-70.
133. • Soontornniyomkij V, Moore DJ, Gouaux B, et al. Cerebral beta-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE epsilon4 carriers. AIDS. 2012;26:2327-35. This clinicopathological study of brain specimens from the National neuroAIDS Tissue Consortium modeled beta-amyloid deposition in subjects with and without HAND on APOE epsilon-4 genotype, older age, and other predictors.
134. Weber E, Morgan EE, Iudicello JE, et al. Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection. J Neurovirol. 2013;19:65-74.
135. • Huidobro C, Fernandez AF, Fraga MF. The role of genetics in the establishment and maintenance of the epigenome. Cell Mol Life Sci. 2013;70:1543-73. This article reviews the evidence for genetic regulation of epigenetic modifications and discusses their contribution to human genetic diseases.
136. Crowell CS, Malee KM, Yogev R,MullerWJ. Neurologic disease in HIV-infected children and the impact of combination antiretroviral therapy. Rev Med Virol. 2014. doi:10.1002/rmv.1793.
137. Hestad KA,Menon JA, Silalukey-Ngoma M, et al. Sex differences in neuropsychological performance as an effect of human immunodeficiency virus infection: a pilot study in Zambia. Africa J Nerv Ment Dis. 2012;200:336-42.
138. Martin E. Substance dependence and NeuroAIDS. Clinical Neuropsychologist. 2005;19:559-60.
139. Blackstone K, Moore DJ, Franklin DR, et al. Defining neurocognitive impairment in HIV: deficit scores versus clinical ratings. Clin Neuropsychol. 2012;26:894-908.
140. Tarr PE, Telenti A. Genetic screening for metabolic and agerelated complications in HIV-infected persons. F1000 medicine reports. 2010;2:83.
141. Valcour VG. Evaluating cognitive impairment in the clinical setting: practical screening and assessment tools. Topics Antiviral Medicine. 2011;19:175-80.
142. • Grant I, Franklin DR, Jr., Deutsch R, et al. Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology. 2014 May 9. [Epub ahead of print]. Very recent longitudinal study in a subset of intensively phenotyped participants from the CHARTER cohort that definitively addresses clinical relevance of ANI: rates of decline to symptomatic HAND were much higher in subjects with ANI versus normal neurocognitive function at baseline.
143. • Cassol E, Misra V, Morgello S, Gabuzda D. Applications and limitations of inflammatory biomarkers for studies on neurocognitive impairment in HIV infection. J Neuroimmune Pharmacol. 2013;8:1087-97. This paper reviews promising biomarkers for HAND and introduces a systems-analysis pipeline to reduce common sources of noise and more easily identify relevant biomarkers.
144. • Holman AG, Gabuzda D. A machine learning approach for identifying amino acid signatures in the HIV env gene predictive of dementia. PLoS One. 2012;7:e49538. This paper discusses the use of machine learning tools for analyzing "omics" data, to identify and validate signatures predictive of HAND.
145. • Foo JN, Liu JJ, Tan EK. Whole-genome and whole-exome sequencing in neurological diseases. Nat Rev Neurol. 2012;8:508-17. This paper discusses the challenges of identifying rare and common variants that play a role in complex neurodegenerative diseases and the use of massively parallel, whole-genomic and whole-exomic sequencing technologies to further personalized medicine in this area.
146. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.
147. Choi M, Scholl UI, Ji WZ, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A. 2009;106:19096-101.
148. Moore DJ, Masliah E, Rippeth JD, et al. Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment. AIDS. 2006;20:879-87. (Pubitemid 43731570)
149. Bertrand SJ, Mactutus CF, Aksenova MV, Espensen-Sturges TD, Booze RM. Synaptodendritic recovery following HIV Tat exposure: neurorestoration by phytoestrogens. J Neurochem. 2014;128:140-51.
150. • Jahanshad N, Rajagopalan P, Thompson PM. Neuroimaging, nutrition, and iron-related genes. Cell Mol Life Sci. 2013;70:4449-61. This study reviews the role of neuroimaging as a means of identifying associations between genetic variations in highly regulated processes such as iron metabolism, brain structural integrity, and cognition.
151. • Chang L, Jiang C, Cunningham E, et al. Effects of APOE epsilon4, age, and HIV on glial metabolites and cognitive deficits. Neurology. 2014;82:2213 - 22. A cross-sectional study investigating the joint effects of HIV and APOE ε 4 genotype on glial metabolite levels and neurocognitive function in HIV-infected individuals.