Top

Published in:

01-08-2014

Discordant patterns of tissue-specific genetic characteristics in the HIV-1 env gene from HIV-associated neurocognitive disorder (HAND) and non-HAND patients

Authors: Yabo Ouyang, Lifeng Liu, Yulin Zhang, Lin Yuan, Zhiying Liu, Sufang Yang, Feili Wei, Luxin Qiao, Dexi Chen

Published in: Journal of NeuroVirology | Issue 4/2014

Abstract

The genetic evolution of HIV-1 in the central nervous system (CNS) is different from that in peripheral tissues. We analyzed 121 clonal sequences of the V3–V5 regions of the env gene generated from paired cerebrospinal fluid (CSF) and plasma samples from nine chronically infected patients (four with HIV-associated neurocognitive disorder (HAND) and five without HAND). The sequence analysis indicated the significant differences between CSF and plasma was only observed in the C4 region (P = 0.043) in HAND patients. Significant increases in synonymous substitutions (dS) within the V4 region (P = 0.020) and in nonsynonymous substitutions (dN) within the C4 region (P = 0.029) were observed in the CSF-derived sequences. By contrast, CSF-derived sequences from non-HAND patients showed similar levels of diversity; dS and dN as the plasma-derived sequences. Signature differences between the CSF- and plasma-derived sequences were found at 12 amino acid positions for HAND patients and nine positions for non-HAND patients. Interestingly, five sites (positions 388, 396, 397, 404, and 406) that all belong to signature patterns exhibited positive selection pressure in CSF samples, but only site 406 was positively selected in the plasma samples from the HAND patients. Conversely, in the non-HAND patients, there were four sites (positions 397, 404, 432, and 446) showed positive selection pressure in the plasma samples, but only site 446 in the CSF samples. These results suggest that discordant patterns of genetic evolution occur between the tissue-specific HIV-1 quasispecies in the HAND and non-HAND patients. Viral molecular heterogeneity between specific tissues is greater in patients with HAND compared to non-HAND patients.

Antinori A, Perno CF, Giancola ML, Forbici F, Ippolito G, Hoetelmans RM, Piscitelli SC (2005) Efficacy of cerebrospinal fluid (CSF)-penetrating antiretroviral drugs against HIV in the neurological compartment: different patterns of phenotypic resistance in CSF and plasma. Clin Infect Dis 41:1787–1793PubMedCrossRef

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedCrossRef

Bonhoeffer S, Holmes EC, Nowak MA (1995) Causes of HIV diversity. Nature 376:125PubMedCrossRef

Derdeyn CA, Decker JM, Bibollet-Ruche F, Mokili JL, Muldoon M, Denham SA, Heil ML, Kasolo F, Musonda R, Hahn BH, Shaw GM, Korber BT, Allen S, Hunter E (2004) Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303:2019–2022PubMedCrossRef

Dunfee RL, Thomas ER, Gorry PR, Wang J, Taylor J, Kunstman K, Wolinsky SM, Gabuzda D (2006) The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci U S A 103:15160–15165PubMedCentralPubMedCrossRef

Dunfee RL, Thomas ER, Wang J, Kunstman K, Wolinsky SM, Gabuzda D (2007) Loss of the N-linked glycosylation site at position 386 in the HIV envelope V4 region enhances macrophage tropism and is associated with dementia. Virology 367:222–234PubMedCentralPubMedCrossRef

Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8:33–44PubMedCrossRef

Harrington PR, Schnell G, Letendre SL, Ritola K, Robertson K, Hall C, Burch CL, Jabara CB, Moore DT, Ellis RJ, Price RW, Swanstrom R (2009) Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course. AIDS 23:907–915PubMedCentralPubMedCrossRef

Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16PubMedCentralPubMedCrossRef

Hightower GK, Wong JK, Letendre SL, Umlauf AA, Ellis RJ, Ignacio CC, Heaton RK, Collier AC, Marra CM, Clifford DB, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Grant I, Little SJ, Richman DD, Kosakovsky PS, Smith DM (2012) Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment. Virology 433:498–505PubMedCentralPubMedCrossRef

Liu Y, Tang XP, McArthur JC, Scott J, Gartner S (2000) Analysis of human immunodeficiency virus type 1 gp160 sequences from a patient with HIV dementia: evidence for monocyte trafficking into brain. J Neurovirol 6(Suppl 1):S70–S81PubMed

Liu L, Zhao Q, Wei F, Yuan L, Zhang Y, Qiao L, Shi Y, Li N, Chen D (2012) Genetic analysis of HIV type 1 env gene in cerebrospinal fluid and plasma of infected Chinese paid blood donors. AIDS Res Hum Retrov 28:106–109CrossRef

Lu L, Jia M, Ma Y, Yang L, Chen Z, Ho DD, Jiang Y, Zhang L (2008) The changing face of HIV in China. Nature 455:609–611PubMedCrossRef

Malherbe DC, Sanders RW, van Gils MJ, Park B, Gomes MM, Schuitemaker H, Barnett S, Haigwood NL (2013) HIV-1 envelope glycoprotein resistance to monoclonal antibody 2G12 is subject-specific and context-dependent in macaques and humans. PLoS One 8:e75277PubMedCentralPubMedCrossRef

Misra A, Ganesh S, Shahiwala A, Shah SP (2003) Drug delivery to the central nervous system: a review. J Pharm Pharm Sci 6:252–273PubMed

Nottet HS, Persidsky Y, Sasseville VG, Nukuna AN, Bock P, Zhai QH, Sharer LR, McComb RD, Swindells S, Soderland C, Gendelman HE (1996) Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain. J Immunol 156:1284–1295PubMed

Ohagen A, Devitt A, Kunstman KJ, Gorry PR, Rose PP, Korber B, Taylor J, Levy R, Murphy RL, Wolinsky SM, Gabuzda D (2003) Genetic and functional analysis of full-length human immunodeficiency virus type 1 env genes derived from brain and blood of patients with AIDS. J Virol 77:12336–12345PubMedCentralPubMedCrossRef

Ouyang Y, Shao Y, Ma L (2012) HIV-1 CRF_BC recombinants infection in China: molecular epidemic and characterizations. Curr HIV Res 10:151–161PubMedCrossRef

Pillai SK, Pond SL, Liu Y, Good BM, Strain MC, Ellis RJ, Letendre S, Smith DM, Gunthard HF, Grant I, Marcotte TD, McCutchan JA, Richman DD, Wong JK (2006) Genetic attributes of cerebrospinal fluid-derived HIV-1 env. Brain 129:1872–1883PubMedCrossRef

Pond SL, Frost SD, Grossman Z, Gravenor MB, Richman DD, Brown AJ (2006) Adaptation to different human populations by HIV-1 revealed by codon-based analyses. PLoS Comput Biol 2:e62PubMedCrossRef

Power C, McArthur JC, Johnson RT, Griffin DE, Glass JD, Perryman S, Chesebro B (1994) Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J Virol 68:4643–4649PubMedCentralPubMed

Power C, McArthur JC, Nath A, Wehrly K, Mayne M, Nishio J, Langelier T, Johnson RT, Chesebro B (1998) Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients. J Virol 72:9045–9053PubMedCentralPubMed

Resch W, Hoffman N, Swanstrom R (2001) Improved success of phenotype prediction of the human immunodeficiency virus type 1 from envelope variable loop 3 sequence using neural networks. Virology 288:51–62PubMedCrossRef

Rong R, Bibollet-Ruche F, Mulenga J, Allen S, Blackwell JL, Derdeyn CA (2007) Role of V1V2 and other human immunodeficiency virus type 1 envelope domains in resistance to autologous neutralization during clade C infection. J Virol 81:1350–1359PubMedCentralPubMedCrossRef

Rossi F, Querido B, Nimmagadda M, Cocklin S, Navas-Martin S, Martin-Garcia J (2008) The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Retrovirology 5:89PubMedCentralPubMedCrossRef

Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, Robertson K, McArthur JC, Ronald A, Katabira E (2005) The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS 19:1367–1374PubMed

Sagar M, Wu X, Lee S, Overbaugh J (2006) Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J Virol 80:9586–9598PubMedCentralPubMedCrossRef

Scanlan CN, Pantophlet R, Wormald MR, Ollmann SE, Stanfield R, Wilson IA, Katinger H, Dwek RA, Rudd PM, Burton DR (2002) The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1→2 mannose residues on the outer face of gp120. J Virol 76:7306–7321PubMedCentralPubMedCrossRef

Schnell G, Price RW, Swanstrom R, Spudich S (2010) Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. J Virol 84:2395–2407PubMedCentralPubMedCrossRef

Soulie C, Tubiana R, Simon A, Lambert-Niclot S, Malet I, Canestri A, Brunet C, Murphy R, Katlama C, Calvez V, Marcelin AG (2009) Presence of HIV-1 R5 viruses in cerebrospinal fluid even in patients harboring R5X4/X4 viruses in plasma. J Acquir Immune Defic Syndr 51:60–64PubMedCrossRef

Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739PubMedCentralPubMedCrossRef

Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, Sullivan N, Srinivasan K, Sodroski J, Moore JP, Katinger H (1996) Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol 70:1100–1108PubMedCentralPubMed

UNAIDS (2011) HIV in China: facts and figures

van Marle G, Power C (2005) Human immunodeficiency virus type 1 genetic diversity in the nervous system: evolutionary epiphenomenon or disease determinant? J Neurovirol 11:107–128PubMedCrossRef

Van Marle G, Rourke SB, Zhang K, Silva C, Ethier J, Gill MJ, Power C (2002) HIV dementia patients exhibit reduced viral neutralization and increased envelope sequence diversity in blood and brain. AIDS 16:1905–1914PubMedCrossRef

Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, Komarova NL, Nowak MA, Hahn BH, Kwong PD, Shaw GM (2003) Antibody neutralization and escape by HIV-1. Nature 422:307–312PubMedCrossRef

Wei F, Wang X, Liu L, Gao R, Shi Y, Zhang Y, Qiao L, Chen D (2011) Characterization of HIV type 1 env gene in cerebrospinal fluid and blood of infected Chinese patients. AIDS Res Hum Retrov 27:793–796CrossRef

Zhang M, Gaschen B, Blay W, Foley B, Haigwood N, Kuiken C, Korber B (2004) Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14:1229–1246PubMedCrossRef

Zhang Y, Qiao L, Ding W, Wei F, Zhao Q, Wang X, Shi Y, Li N, Smith D, Chen D (2012a) An initial screening for HIV-associated neurocognitive disorders of HIV-1 infected patients in China. J Neurovirol 18:120–126PubMedCrossRef

Zhang Y, Wang M, Li H, Zhang H, Shi Y, Wei F, Liu D, Liu K, Chen D (2012b) Accumulation of nuclear and mitochondrial DNA damage in the frontal cortex cells of patients with HIV-associated neurocognitive disorders. Brain Res 1458:1–11PubMedCrossRef

Zhang Y, Wei F, Liang Q, Ding W, Qiao L, Song F, Liu L, Yang S, Jin R, Gu J, Li N, Chen D (2013) High levels of divergent HIV-1 quasispecies in patients with neurological opportunistic infections in China. J Neurovirol 19:359–366PubMedCrossRef

Title: Discordant patterns of tissue-specific genetic characteristics in the HIV-1 env gene from HIV-associated neurocognitive disorder (HAND) and non-HAND patients
Authors: Yabo Ouyang
Lifeng Liu
Yulin Zhang
Lin Yuan
Zhiying Liu
Sufang Yang
Feili Wei
Luxin Qiao
Dexi Chen
Publication date: 01-08-2014
Publisher: Springer US
Published in: Journal of NeuroVirology / Issue 4/2014
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-014-0247-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Discordant patterns of tissue-specific genetic characteristics in the HIV-1 env gene from HIV-associated neurocognitive disorder (HAND) and non-HAND patients

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2014

Glutamate metabolism and HIV-associated neurocognitive disorders

Prevalence of human Herpesviridae in cerebrospinal fluid of patients with multiple sclerosis and noninfectious neurological disease in the Netherlands

Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals

Histopathology and immunohistochemistry of tissues outside central nervous system in bovine rabies

Neurocognitive impairment associated with predominantly early stage HIV infection in Abuja, Nigeria

Acute Human T-lymphotropic virus type I-associated myelitis: a rare case successfully treated with intravenous pulse methylprednisolone