Journal of NeuroVirology

, Volume 19, Issue 4, pp 359–366

High levels of divergent HIV-1 quasispecies in patients with neurological opportunistic infections in China



Despite the fact that the survival of people infected with human immunodeficiency virus (HIV) has improved worldwide because of the increasingly powerful and highly active antiretroviral therapy, opportunistic infections (OIs) of the central nervous system (CNS) remain a serious burden. HIV-1 is capable of entering the CNS through infected peripheral monocytes, but its effect on OIs of CNS remains unclear. In this study, we investigated the characteristics of HIV-1 in acquired immunodeficiency syndrome (AIDS) patients with CNS OIs. A total of 24 patients with CNS OIs and 16 non-CNS OIs (control) cases were selected. These AIDS patients were infected with HIV-1 by paid blood donors in China. HIV-1 loads in plasma and cerebrospinal fluid (CSF) were detected using RT-PCR, and the C2-V5 region of HIV-1 envelope gene was amplified from viral quasispecies isolated from CSF using nested PCR. The CSF HIV-1 load of CNS OIs was higher than that of non-CNS OIs, but plasma HIV-1 load of CNS OIs was not higher than that of non-CNS OIs. The nucleotide sequence of C2-V5 region of the HIV-1 quasispecies isolated from the CSF of CNS OIs had a high diversity, and the HIV-1 quasispecies isolated from the CSF of CNS OIs revealed R5 tropism as 11/25 charge rule. These results suggest that high levels of divergent HIV-1 quasispecies in the CNS probably contribute to opportunistic infections.


AIDS Central nervous system HIV-1 Opportunistic infections Viral tropism 


  1. Bachis A, Biggio F, Major EO, Mocchetti I (2009) M- and T-tropic HIVs promote apoptosis in rat neurons. J Neuroimmune Pharmacol 4:150–60PubMedCrossRefGoogle Scholar
  2. Borda JT, Alvarez X, Mohan M, Hasegawa A, Bernardino A, Jean S, Aye P, Lackner AA (2008) CD163, a marker of perivascular macrophages, is up-regulated by microglia in simian immunodeficiency virus encephalitis after haptoglobin-hemoglobin complex stimulation and is suggestive of breakdown of the blood–brain barrier. Am J Pathol 172:725–37PubMedCrossRefGoogle Scholar
  3. Christo PP, Greco DB, Aleixo AW, Livramento JA (2005) HIV-1 RNA levels in cerebrospinal fluid and plasma and their correlation with opportunistic neurological diseases in a Brazilian AIDS reference hospital. Arq Neuropsiquiatr 63:907–13PubMedGoogle Scholar
  4. Christo PP, Greco DB, Aleixo AW, Livramento JA (2007) Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era. BMC Infect Dis 7:147PubMedCrossRefGoogle Scholar
  5. Christo PP, Vilela Mde C, Bretas TL, Domingues RB, Greco DB, Livramento JA, Teixeira AL (2009) Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system. J Neurol Sci 287:79–83PubMedCrossRefGoogle Scholar
  6. Chun H, Hao W, Honghai Z, Ning L, Yasong W, Chen D (2009) CCL3L1 prevents gp120-induced neuron death via the CREB cell signaling pathway. Brain Res 1257:75–88PubMedCrossRefGoogle Scholar
  7. COHERE (2012) CD4 cell count and the risk of AIDS or death in HIV-infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE. PLoS Med 9:e1001194CrossRefGoogle Scholar
  8. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–5PubMedCrossRefGoogle Scholar
  9. Goodenow MM, Collman RG (2006) HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes. J Leukoc Biol 80:965–72PubMedCrossRefGoogle Scholar
  10. Haase AT (1986) Pathogenesis of lentivirus infections. Nature 322:130–6PubMedCrossRefGoogle Scholar
  11. Jensen MA, van 't Wout AB (2003) Predicting HIV-1 coreceptor usage with sequence analysis. AIDS Rev 5:104–12PubMedGoogle Scholar
  12. Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H (2009) Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58: 1–207; quiz CE1-4.Google Scholar
  13. Kim WK, Alvarez X, Fisher J, Bronfin B, Westmoreland S, McLaurin J, Williams K (2006) CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. Am J Pathol 168:822–34PubMedCrossRefGoogle Scholar
  14. 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 Retroviruses 28:106–9PubMedCrossRefGoogle Scholar
  15. Martin C, Albert J, Hansson P, Pehrsson P, Link H, Sonnerborg A (1998) Cerebrospinal fluid mononuclear cell counts influence CSF HIV-1 RNA levels. J Acquir Immune Defic Syndr Hum Retrovirol 17:214–9PubMedCrossRefGoogle Scholar
  16. Masur H, Kaplan JE (2009) New guidelines for the management of HIV-related opportunistic infections. JAMA 301:2378–80PubMedCrossRefGoogle Scholar
  17. Mocroft AJ, Lundgren JD, D'Armino Monforte A, Ledergerber B, Barton SE, Vella S, Katlama C, Gerstoft J, Pedersen C, Phillips AN (1997) Survival of AIDS patients according to type of AIDS-defining event. The AIDS in Europe Study Group. Int J Epidemiol 26:400–7PubMedCrossRefGoogle Scholar
  18. Perry VH, Nicoll JA, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6:193–201PubMedCrossRefGoogle Scholar
  19. Riveiro-Barciela M, Falco V, Burgos J, Curran A, Van den Eynde E, Navarro J, Villar Del Saz S, Ocana I, Ribera E, Crespo M, Pahissa A (2013) Neurological opportunistic infections and neurological immune reconstitution syndrome: impact of one decade of highly active antiretroviral treatment in a tertiary hospital. HIV Med 14:21–30Google Scholar
  20. Saitoh A, Fenton T, Alvero C, Fletcher CV, Spector SA (2007) Impact of nucleoside reverse transcriptase inhibitors on mitochondria in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy. Antimicrob Agents Chemother 51:4236–42PubMedCrossRefGoogle Scholar
  21. Soulas C, Conerly C, Kim WK, Burdo TH, Alvarez X, Lackner AA, Williams KC (2011) Recently infiltrating MAC387(+) monocytes/macrophages a third macrophage population involved in SIV and HIV encephalitic lesion formation. Am J Pathol 178:2121–35PubMedCrossRefGoogle Scholar
  22. Soulas C, Donahue RE, Dunbar CE, Persons DA, Alvarez X, Williams KC (2009) Genetically modified CD34+ hematopoietic stem cells contribute to turnover of brain perivascular macrophages in long-term repopulated primates. Am J Pathol 174:1808–17PubMedCrossRefGoogle Scholar
  23. Soulie C, Fourati S, Lambert-Niclot S, Tubiana R, Canestri A, Girard PM, Katlama C, Morand-Joubert L, Calvez V, Marcelin AG (2010) HIV genetic diversity between plasma and cerebrospinal fluid in patients with HIV encephalitis. AIDS 24:2412–4PubMedGoogle Scholar
  24. Spudich S, Gonzalez-Scarano F (2012) HIV-1-related central nervous system disease: current issues in pathogenesis, diagnosis, and treatment. Cold Spring Harb Perspect Med 2:a007120PubMedCrossRefGoogle Scholar
  25. Tan IL, Smith BR, von Geldern G, Mateen FJ, McArthur JC (2012) HIV-associated opportunistic infections of the CNS. Lancet Neurol 11:605–17PubMedCrossRefGoogle Scholar
  26. van Marle G, Power C (2005) Human immunodeficiency virus type 1 genetic diversity in the nervous system: evolutionary epiphenomenon or disease determinant? J Neurovirol 11:107–28PubMedCrossRefGoogle Scholar
  27. 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 Retroviruses 27:793–6PubMedCrossRefGoogle Scholar
  28. Wu Z, Sun X, Sullivan SG, Detels R (2006) Public health. HIV testing in China Science 312:1475–6Google Scholar
  29. 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 18:120–6PubMedCrossRefGoogle Scholar
  30. 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 1458:1–11PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2013

Authors and Affiliations

  1. 1.Department of Infectious Diseases, Beijing You’An HospitalCapital Medical UniversityBeijingChina
  2. 2.Department of LaboratoryAffiliated Hospital of North Sichuan Medical CollegeNanchongChina
  3. 3.Beijing Institute of HepatologyCapital Medical UniversityBeijingChina
  4. 4.Department of Medicine, Jiangsu Geriatrics InstituteJiangsu Geriatric HospitalNanjingChina
  5. 5.STD AIDS Research Center, Beijing Key Laboratory (No. BZ0089), Beijing You’An Hospital, Beijing Institute of HepatologyCapital Medical UniversityBeijingChina

Personalised recommendations