PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of molmedLink to Publisher's site
 
Mol Med. 1996 May; 2(3): 358–366.
PMCID: PMC2230156

AIDS dementia is associated with massive, activated HIV-1 infection and concomitant expression of several cytokines.

Abstract

BACKGROUND: We recently showed that acquired immunodeficiency syndrome (AIDS) dementia is associated with activated infection of microglia, neurons, and astrocytes by HIV-1. However, it is doubtful whether infection per se is responsible for the dramatic symptoms associated with AIDS dementia. The purpose of this study was to determine the histologic distribution of messenger RNAs (mRNAs) of several cytokines that have been implicated in AIDS pathogenesis and to correlate this expression pattern with the in situ localization of polymerase chain reaction (PCR)-amplified HIV-1 nucleic acids in the central nervous system (CNS). MATERIALS AND METHODS: HIV-1 DNA was detected by PCR in situ hybridization. HIV-1 RNA and cytokine expression, including tumor necrosis factor alpha (TNF), inducible nitric oxide synthetase (iNOS), and macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta mRNA were detected by reverse transcriptase (RT) in situ PCR. RESULTS: Amplified viral DNA was detected in each of the seven HIV-1-positive cases and in none of the five negative controls. In people with AIDS dementia, many HIV-1 DNA-positive cells were detected in regions of the CNS that corresponded to clinical symptomatology. In AIDS patients with minimal CNS involvement, rare HIV-1-infected microglial cells were noted. Viral RNA was detected primarily in cases of AIDS dementia. TNF, iNOS, MIP-1 alpha and MIP-1 beta expression localized to tissues from AIDS dementia cases where HIV-1 infected cells were plentiful. Colocalization experiments showed that these cytokines were transcribed mostly by viral-negative cells. CONCLUSIONS: These results suggest that two key elements in AIDS dementia are massive productive viral infection, involving microglia, neurons, and astrocytes, and concomitant stimulation of cytokine transcription in the neighboring uninfected cells.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science. 1988 Feb 5;239(4840):586–592. [PubMed]
  • Grant I, Atkinson JH, Hesselink JR, Kennedy CJ, Richman DD, Spector SA, McCutchan JA. Evidence for early central nervous system involvement in the acquired immunodeficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Studies with neuropsychologic testing and magnetic resonance imaging. Ann Intern Med. 1987 Dec;107(6):828–836. [PubMed]
  • Weiser B, Peress N, La Neve D, Eilbott DJ, Seidman R, Burger H. Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. Proc Natl Acad Sci U S A. 1990 May;87(10):3997–4001. [PubMed]
  • Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089–7093. [PubMed]
  • Tornatore C, Nath A, Amemiya K, Major EO. Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta. J Virol. 1991 Nov;65(11):6094–6100. [PMC free article] [PubMed]
  • Watkins BA, Dorn HH, Kelly WB, Armstrong RC, Potts BJ, Michaels F, Kufta CV, Dubois-Dalcq M. Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science. 1990 Aug 3;249(4968):549–553. [PubMed]
  • Cvetkovich TA, Lazar E, Blumberg BM, Saito Y, Eskin TA, Reichman R, Baram DA, del Cerro C, Gendelman HE, del Cerro M, et al. Human immunodeficiency virus type 1 infection of neural xenografts. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5162–5166. [PubMed]
  • Harouse JM, Bhat S, Spitalnik SL, Laughlin M, Stefano K, Silberberg DH, Gonzalez-Scarano F. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science. 1991 Jul 19;253(5017):320–323. [PubMed]
  • Nuovo GJ, Gallery F, MacConnell P, Braun A. In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acids and tumor necrosis factor-alpha RNA in the central nervous system. Am J Pathol. 1994 Apr;144(4):659–666. [PubMed]
  • Lipton SA. HIV-related neurotoxicity. Brain Pathol. 1991 Apr;1(3):193–199. [PubMed]
  • Yamada M, Zurbriggen A, Oldstone MB, Fujinami RS. Common immunologic determinant between human immunodeficiency virus type 1 gp41 and astrocytes. J Virol. 1991 Mar;65(3):1370–1376. [PMC free article] [PubMed]
  • Dubrovsky L, Ulrich P, Nuovo GJ, Manogue KR, Cerami A, Bukrinsky M. Nuclear localization signal of HIV-1 as a novel target for therapeutic intervention. Mol Med. 1995 Jan;1(2):217–230. [PMC free article] [PubMed]
  • Nuovo GJ, Becker J, Burk MW, Margiotta M, Fuhrer J, Steigbigel RT. In situ detection of PCR-amplified HIV-1 nucleic acids in lymph nodes and peripheral blood in patients with asymptomatic HIV-1 infection and advanced-stage AIDS. J Acquir Immune Defic Syndr. 1994 Sep;7(9):916–923. [PubMed]
  • Bagasra O, Hauptman SP, Lischner HW, Sachs M, Pomerantz RJ. Detection of human immunodeficiency virus type 1 provirus in mononuclear cells by in situ polymerase chain reaction. N Engl J Med. 1992 May 21;326(21):1385–1391. [PubMed]
  • Seshamma T, Bagasra O, Oakes JW, Pomerantz RJ. A quantitative reverse transcriptase-polymerase chain reaction for HIV-1-specific RNA species. J Virol Methods. 1992 Dec 1;40(3):331–345. [PubMed]
  • Dawson VL, Dawson TM, London ED, Bredt DS, Snyder SH. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6368–6371. [PubMed]
  • Buttery LD, Evans TJ, Springall DR, Carpenter A, Cohen J, Polak JM. Immunochemical localization of inducible nitric oxide synthase in endotoxin-treated rats. Lab Invest. 1994 Nov;71(5):755–764. [PubMed]
  • Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MA. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science. 1994 Sep 23;265(5180):1883–1885. [PubMed]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ