Conclusion
The immunopathogenesis of AIDS is a product of host and viral genetics, immune activation, and environmental conditions. Exposed individuals either become infected or resist infection based on the interactions of these factors. Among those infected, their capacity to transmit the virus, their rate of disease progression, and their clinical prognosis also depend upon multiple factors. We have come to understand that HLA alleles and their cognate T-cell epitopes; cellular and humoral immune responses; and chemokine receptor polymorphisms and mutations each play a role in the immunopathogenesis of HIV-1 infection. The immune response within an individual and a population may select for the transmission, replication, and the relative success of certain viral subtypes and circulating recombinant forms (194). Immune responses, conditioned by HLA alleles inherited from each parent and chemokine receptor genes, exert negative and positive selection pressures on viruses for their expression of antigens and their susceptibility to various arms of the immune system. In Africa, these interactions between host and pathogen take place in individuals and populations who may be more vulnerable to infection due to nutritional deficiencies and chronic parasitic infections with concomitant immune hyperactivation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Fauci AS. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science, 1988;239:617–622.
Fauci AS. Multifactorial nature of human immunodeficiency virus disease implications for therapy. Science, 1993;262:1011–1018.
Fauci AS. Host factors and the pathogenesis of HIV-1 induced disease. Nature, 1996;384:529–534.
Cao Y, Qin L, Zhang L, et al. Virologic and immunologic characterization of long term survivors of human immunodeficiency virus type 1 infection. N Engl J Med, 1995:332:301–330.
Pantaleo G, Menzo S, Vaccarezza M, et al. Studies in subjects with long-term nonprogressive HIV infection. N Engl J Med, 1995;332:209–216.
Pantaleo G, Graziosi C, Demarest JF, et al. HIV Infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature, 1993;362:355–358.
Alexander L, Weiskopf E, Greenough TC, et al. Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection. J Virol, 2000;74:4361–4376.
Greenough TC, Brettler DB, Somasundaran DL. Human immundoeficiency virus type 1-specific cytotoxic T lymphocytes (CTL) virus load and CD4 cell loss: evidence supporting a protective role of CTL in vivo. J Infect Dis, 1997;176:118–125.
Rivets H, Marissens D, De Wit S, et al. Comparative Evaluation of NASBA HIV-1 RNA QT, AMPLICOR-HIV Monitor, and QUANTIPLEX HIV RNA Assay, Three Methods for Quantification of Human Immunodeficiency Virus Type 1 RNA in Plasma. J Clin Microbiol, 1996;34:1058–1064.
Piatak M, Saag MS, Yang LC, et al. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science, 1993;259:1749–1754.
Henrard DR, Daar E, Farzadegan H, et al. Virologic and immunologic characterizations of symptomatic and asymptomatic primary HIV-1 infection. J Acq. Imm Def Synd Hum Retro, 1995;9:305–310.
Mellors JW, Muanoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med, 1997;126:946–954.
Miller V, Mocroft A, Reiss P, et al. Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study. Ann Intern Med, 1999;130:570–577.
Morgan D, Rutemberwa A, Malamba S, et al. HIV-1 RNA levels in an African populationbased cohort and their relation to CD4 lymphocyte counts and World Health Organization clinical staging. J Acquir Immune Defic Syndr, 1999;22:167–173.
Taha TE, Kumwenda NI, Hoover DR, et al. Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age. AIDS, 2000; 10;14:453–459.
Kassa E, Rinke de Wit TF, Hailu E, et al. Evaluation of the World Health Organization staging system for HIV infection and disease in Ethiopia: association between clinical stages and laboratory markers. AIDS, 1999;13:381–389.
van der Ryst E, Kotze M, Joubert G, et al. Correlation among total lymphocyte count, absolute CD4+ count, and CD4+ percentage in a group of HIV-1-infected South African patients. J. Acquir Immune Defic Syndr Hum Retrovirol, 1998;19:238–244.
Rinaldo C, Huang XL, Fan ZF, et al. High levels of anti-human immundoeficiency virus type 1 memory cytotoxic T-lymphocyte activity and low virus load are associated with lack of disease in HIV-1-infected long-term non-progressors. J Virol, 1995;69:5838–5842.
Rosenberg ES, Billingsley JM, Caliendo AM, et al. Vigorous HIV-1 specific CD4+ T cell responses associated with control of viremia. Science, 1997;278:1447–1450.
Gourgeon ML, Montagnier L. Apoptosis in AIDS [published erratum in Science, 1993;260:1709]. Science, 1993;260:1269–1270.
Finkel TH, Tudor-Williams G, Banda NK, et al. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV-and SIV-infected lymph nodes. Nat Med, 1995;129–134.
Lane HC, Masur H, Edgar LC, et al. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N. Engl J Med, 1983;309:453–458.
Martinez-Maza O, Crabb E, Mitsyuasu RT, et al. Infection with human immunodeficiency virus (HIV) is associated with an in vivo increase in B lymphocyte activation and immaturity. J Immunol, 1987;138:3720–3724.
Katzenstein DA, Latif AS, Grace A, et al. Clinical and laboratory characteristics of HIV-1 infection in Zimbabwe. J Acquir Immune Defic Syndr Hum. Retrovirol, 1990;3:701–701.
Wilcock G, Grace S, De Villiers D, et al. Karposi’s sarcoma in Zimbabwe. II. Peripheral lymphocytes, immunoglobulin G levels, and HIV positivity. J Clin Lab Immunol, 1998;27:25028.
Munoz A, Carey V, Saah AJ, et al. Predictors of decline in CD4 lymphocytes in a cohort of homosexual men infected with human immunodeficiency virus. J Acquir Immune Defic Syndr Hum. Retrovirol, 1988;1:396–404.
Fahey JL, Taylor JMG, Detels R, et al. The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type I. N. Engl J Med, 1990;322:166–172.
Moss AR, Bacchetti P, Osmond D, et al. Seropositivity for HIV and the development of AIDS or AIDS related condition: three year follow up of the San Francisco cohort. Br Med J, 1988;296:745–750.
Lacey JN, Forbes MA, Waugh MA, et al. Serum beta2-microglobulin and human immunodeficiency virus infection. AIDS, 1997;1:123–127.
Hofmann B, Wang Y, Cumberland WG, et al. Immune activation by HIV: seroconversion and progression in serum beta2-microglobulin. AIDS, 1990;4:207–214.
Fuchs D, Hausen A, Reignegger G, et al. Neopterin as a marker for activated cell mediated immunity: application in HIV infection. Immunol Today, 1988;9:150–155.
Ziegler I, Rokos H. Pteridines and the immune response. J Immunol Immunopharm, 1986;6:169–177.
Melmed RN, Taylor JM, Detels R, et al. Serum neopterin changes in HIV-infected subjects: indicator of significant pathology, CD4 T cell change, and the development of AIDS. J Acquir Immune Defic. Syndr, 1989;2:70–76.
Dyer JR, Eron JJ, Hoffman IF, et al. Association of CD4 cell depletion and elevated blood and seminal plasma human immunodeficiency virus type 1 (HIV-1) RNA concentrations with genital ulcer disease in HIV-1-infected men in Malawi. J Infect. Dis, 1998; 177:224–227.
McCune JM, Hanley MB, Cesar D, et al. Factors influencing T-cell turnover in HIV-1 seropositive patients. J Clin Invest, 1999;105:R1–R8.
Grant AD, Djomand G, De Cock KM. Natural history and spectrum of disease in adults with HIV/AIDS in Africa. AIDS, 1997;11Suppl B:S43–S54.
Wood R, Maartens G, Lombard CJ. Risk factors for developing tuberculosis in HIV-1-infected adults from communities with a low or very high incidence of tuberculosis. J Acquir Immune Defic. Syndr, 2000;23:75–80.
Bentwich Z, Kalinkovich A, Weisman Z. Immune activation is a dominant factor in the pathogenesis of African AIDS. Immunol Today, 1995;16:187–91.
Migot F, Ouedraogo JB, Diallo J, et al. Selected P. falciparum specific immune responses are maintained in AIDS adults in Burkina Faso. Parasite Immunol, 1996;18:333–339.
Gopinath R, Ostrowski M, Justement SJ, et al. Filarial infections increase susceptibility to human immunodeficiency virus infection in peripheral blood mononuclear cells in vitro. J Infect Dis, 2000;182:1804–1808.
Berneir RS, Turco J, Olivier M, Tremblay M. Acitvation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite Leishmania donovani. J Virol, 1995;69:7282–7285.
Rizzardini G, Trabattoni D, Saresella M, et al. Immune activation in HIV-infected African individuals. Italian-Ugandan AIDS cooperation program. AIDS, 1998;12:2387–2396.
Messele T, Abdulkadir M, Fontanet AL et al. Reduced naive and increased activated CD4 and CDS cells in healthy adult Ethiopians compared with their Dutch counterparts. Clin Exp Immunol, 1999;115:443–450.
Weisman Z, Kalinkovich A, Borkow G et al. Infection by different HIV-1 subtypes (B and C) results in a similar immune activation profile despite distinct immune backgrounds. J Acquir. Immune Defic Syndr, 1999;21:157–163.
Weissman D, Barker TD, Fauci AS. The efficiency of acute infection of CD4+T cells is markedly enhanced in the setting of antigen-specific immune activation. J Exp Med, 1996; 183:687–692.
Whitworth J, Morgan D, Quigley M et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet, 2000;356:1051–1056.
French N, Gilks CF. Royal Society of Tropical Medicine and Hygiene meeting at Manson House, London, 18 March 1999. Fresh from the field: some controversies in tropical medicine and hygiene. HIV and malaria, do they interact? Trans Royal Soc Trop Med Hyg, 2000;94:233–237.
Antelman G, Msamanga GI, Spiegelman D, et al. Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania. J. Nutr, 2000;130:1950–1957.
Tsegaye A, Messele T, Tilahun T, Immunohematological reference ranges for adult Ethiopians. Clin. Diagn Lab Immunol, 1999;6:410–414.
Bogden JD, Kemp FW, Han S, et al. Status of selected nutrients and progression of human immunodeficiency virus type 1 infection. Am J. Clin Nutr, 2000;2:809–815.
Baum MK, Shor-Posner G, Campa A. Zinc status in human immunodeficiency virus infection. J Nutr, 2000;130(5S Suppl):1421S–1423S.
Dannhauser A, van Staden AM, van der Ryst E, et al. Nutritional status of HIV-1 seropositive patients in the Free State Province of South Africa: anthropometric and dietary profile. Eur J Clin Nutr, 1999;53:165–173.
Fawzi WW, Msamanga GI, Spiegelman D. Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet, 1998;351:1477–1482.
Kelly P, Musonda R, Kafwembe E, Micronutrient supplementation in the AIDS diarrhoea-wasting syndrome in Zambia: a randomized controlled trial. AIDS, 1999;13:495–500.
Ng TT, Pinching AJ, Guntermann C, et al. Molecular immunopathogenesis of HIV infection. Genitourin Med, 1996;72(6):408–18.
Kaul R, Plummer FA, Kimani J, et al. HIV-1 specific CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi. J Immunol, 2000;164:1602–1611.
Rowland-Jones S, Dong T, Fowke KR, et al. Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. J Clin Invest, 1998;102:1758–1765.
Kaul R, Trabattoni D, Bwayo JJ, et al. HIV-specific mucosal IgA in a cohort of HIV-1 resistant Kenyan sex workers. AIDS, 1999;13:23–29.
MacDonald KS, Keith R, Kimani FJ, et al. Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. J Infect Dis, 200;181:1581–1589.
Roger M. Influence of Host genes on HIV-1 progression. FASEB J, 1998;12:625–632.
Carrington M, Nelson GW, Martin MP, et al. HLA and HIV-1: Heterozygote advantage and B*35-Cw*04 disadvantage. Science, 1999;283:1748–1752.
Autran B, Haidida F, Haas G. Evolution and plasticity of CTL responses against HIV Curr Opin Immunol, 1996;8:546–553.
French N, Mujugira A, Nakiyingi J, et al. Immunologic and clinical stages in HIV-1-infected Ugandan adults are comparable and provide no evidence of rapid progression but poor survival with advanced disease. J Acquir Immune Defic Syndr, 1999;22:509–516.
Ho DD, Neuman AU, Perleson AS, et al. Rapid turnover of plasma virions and CD4+ lymphocytes in HIV infection. Nature, 1995:373:123–126.
Wei X, Ghosh, Talylor ME, et al. Viral dymanics in HIV-1 infection. Nature, 1995;373:117–122.
Hellerstein MK, McCune JM. T cell turnover in HIV-1 disease. Immunity, 1997;7:583–598.
Clark DR, de Boer RJ, Wolters KC and Miedma F. T cell dynamics in HIV-1 infection Adv Immunol, 1999;73:301–332.
Autran B, Carcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ T-cell homeostasis and function in advanced HIV disease. Science, 1997;227:112–116.
Lederman MM, Connick E, Landay A, et al. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine and ritonavir. J Infect Dis, 1998;178:70–79.
Richman DD, Normal physiology and HIV pathophysiology of human T-cell dynamics. J Clin Invest, 2000;105:565–566.
Lederman MM, Valdez H. Immune restoration with antiretroviral therapies. JAMA, 2000;284:223–228.
Katzenstein DA, Mbizvo M, Zijenah L, et al. Serum level of maternal human immunodeficiency virus (HIV) RNA, infant mortality, and vertical transmission of HIV in Zimbabwe. J Infect Dis, 1999; 179:1382–1387.
Nunn PP, Brindle R, Carpenter L, et al. Cohort study of HIV infection in patients with tuberculosis in Nairobi, Kenya. Analysis of early (6 mo) mortality. Am Rev Respir Dis, 1992;146:849–854.
Sloand E, Pitt E, Chiarello RJ, Nemo GJ. HIV testing state of the art. JAMA, 1991;266:2861–2866.
van Binsbergen J, de Rijk D, Peels H, et al. Evaluation of a new third generation anti-HIV-1/anti-HIV-2 assay with increased sensitivity for HIV-1 group O. J Virol Methods, 1996;60:131–137.
Frank AP, Wandell MG, Headings MD, et al. Anonymous HIV testing using home collection and telemedicine counseling. A multicenter evaluation. Archives of Int Med, 1997;157:309–314.
Gallo D, George JR, Fitchen JH, et al. Evaluation of a system using oral mucosal transudate for HIV-1 antibody screening and confirmatory testing. JAMA, 1997;277:254–258.
Urnovitz HB, Sturge JC, Gottfried TD, Murphy WH. Urine antibody tests: new insights into the dynamics of HIV-1 infection. Clin Chem, 1999;45;1602–1613.
Janssen RS, Satten GA, Stramer, SL, et al. New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes. JAMA, 1998;280;42–48.
LaCasse RA, Follis KE, Trahey M, et al. Fusioncompetent vaccines: broad neutralization of primary isolates of HIV Science, 1999;283:357–362.
Park EJ, Gorny MK, Zolla-Pazner S, Quinnan GV Jr. A global neutralization resistance phenotype of human immunodeficiency virus type 1 is determined by distinct mechanisms mediating enhanced infectivity and conformational change of the envelope complex. J Virol, 2000;74:4183–4191.
Beirnaert E, Nyambi P, Willems B, et al. Identification and characterization of sera from HIV-infected individuals with broad cross-neutralizing activity against group M (env clade A-H) and group O primary HIV-1 isolates. J Med Virol, 2000;62:14–24.
Fust G. Enhancing antibodies in HIV infection. Parasitology, 1997;115 Suppl:S127–S140.
Ruppach H, Nara P, Raudonat I, et al. Human immunodeficiency virus (HIV)-positive sera obtained shortly after seroconversion neutralize autologous HIV typel isolates on primary macrophages but not on lymphocytes. J Virol, 2000;74:5403–5411.
Lathey JL, Tsou J, Brinker K, et al. Lack of autologous neutralizing antibody to human immunodeficiency virus type 1 (HIV-1) and macrophage tropism are associated with mother-to-infant transmission. J Infect Dis, 1999;180:344–350.
Carotenuto P, Looij D, Keldermans L, de Wolf F, Goudsmit J. Neutralizing antibodies are positively associated with CD4+T-cell counts and T-cell function in long-term AIDS-free infection. AIDS, 1998;12:1591–1600.
Cecilia D, Kleeberger C, Munoz A, Giorgi JV, Zolla-Pazner S. A longitudinal study of neutralizing antibodies and disease progression in HIV-1-infected subjects. J Infect Dis, 1999;179:1365–1374.
Barker E, Mackewicz CE, Reyes-Teran G, et al. Virological and immunological features of long-term human immunodeficiency virus-infected individuals who have remained asymptomatic compared with those who have progressed to acquired immunodeficiency syndrome. Blood, 1998;92:3105–3114.
Jolly PE, Weiss HL. Neutralization and enhancement of HIV-1 infection by sera from HIV-1 infected individuals who progress to disease at different rates. Virology, 2000;273:52–59.
Nokta M, Turk P, Loesch K, Pollard RB. Neutralization profiles of sera from human immunodeficiency virus (HIV)-infected individuals: relationship to HIV viral load and CD4 cell count. Clin. Diagn Lab Immunol, 2000;7:412–416.
Lewis J, Balfe P, Arnold C, et al. Development of a neutralizing antibody response during acute primary human immunodeficiency virus type 1 infection and the emergence of antigenic variants. J. Virol, 1998;72:8943–8951.
Ciurea A, Hunziker L, Klenerman P, et al. Impairment of CD4+ T cell responses during chronic virus infection prevents neutralizing antibody response against virus escape mutants, J Exp. Med, 2001;193:297–305.
Poignard P, Sabbe R, Picchio GR. Neutralizing anti-bodies have limited effects on the control of established HIV-1 infection in vivo. Immunity, 1999; 10:431–438.
Schonning K, Joost M, Gram GJ, et al. Chemokine receptor polymorphism and autologous neutralizing antibody response in long-term HIV-1 infection. J Acquir Immune Defic Syndr Hum. Retrovirol, 1998;18:195–202.
Bradney AP, Scheer S, Crawford JM, et al. Neutralization escape in human immunodeficiency virus type 1-infected long-term nonprogressors. J Infect Dis, 1999;179:1264–1267.
Gea-Banacloche JC, Migueles SA, Martino L, et al. Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. J Immunol, 2000;165:1082–1092.
Salminen MO, Carr JK, Robertson DL, et al. Evolution and probable transmission of intrasubtype recombinant human immunodeficiency virus type 1 in a Zambian couple. J Virol, 1997;71:2647–2655.
MacDonald KS, Embree J, Njenga S, et al. Mother-child class I HLA concordance increases perinatal human immunodeficiency virus type 1 transmission. J Infect Dis, 1998;177:551–556.
Thea DM, Porat R, Nagimbi K, et al. Plasma cytokines, cytokine antagonists, disease progression in African women infected with HIV-1. Ann Intern. Med, 1996;124:757–762.
Sonnerborg A, Ayehunie S, Julander I. Elevated levels of circulating tumor necrosis factor alpha in human immunodeficiency virus type 1-infected Africans living in Sweden. Clin Diagn Lab. Immunol, 1995;2:118–119.
Anzala A, Simonsen J, Kimani J, et al. Acute sexually transmitted infections increase HIV-1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 counts. J Infect Dis, 2000;182:459–466.
Lawn SD, Shattock RJ, Acheampong JW, et al. Sustained plasma TNF-alpha and HIV-1 load despite resolution of other parameters of immune activation during treatment of tuberculosis in Africans. AIDS, 1999;12:2231–2237.
Clouse KA, Powell D, Washington I, et al. Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J. Immunol, 1989;142:431–438.
Osborn L, Kunkel S, Nabel GJ. Tumour necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kB. Proc Natl Acad Sci USA, 1989;2336–2340.
Duh EJ, Maury WJ, Folks TM, et al. Tumour necrosis factor a activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kB sites in the long terminal repeat. Proc Natl Acad Sci USA, 1989;86:5974–5978.
Griffin GE, Leung K, Folks TM, et al. Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B. Nature, 1989;339:70–73.
Franzoso G, Biswas P, Poli G, et al. A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the nuclear factor kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells. J Exp Med, 1994;180:1445–1456.
Siebenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-kB. Ann Rev Cell Biol, 1994;10:405–455.
Gao F, Roberton DL, Morrison SG, et al. The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin. J Virol, 1996;70:7013–7029.
Montano MA, Novitsky VA, Blackard JT, et al. Divergent transcriptional regulation among expanding human immunodeficiency type 1 subtypes. J Virol, 1997;71:8657–8665.
Poli G, Kinter AL, Fauci AS. Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected Ul cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proc Natl Acad Sci USA, 1994;91;108–112.
Kinter AL, Poli G, Fox L, et al. HIV replication in IL-2 stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogenous cytokines. J Immunol, 1995; 2448–2459.
Koyanagi Y, O’Brien WA, Zhao JQ, et al. Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Science, 1988;241:1673–1675.
Poli G, Bressler P, Kinter A, et al. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanism. J Exp Med, 1990; 172:151–158.
Moran PA, Diegel ML, Sias JC, et al. Regulation HIV production by blood mononuclear cells from HIV-infected donors: I. Lack of correlation between HIV-1 production and T cell activation. AIDS Res Hum Retroviruses, 1993;9:455–464.
Al-Harthi L, Roebuck KA, Landay A. Induction of HIV-1 replication by type 1-like cytokines, IL-12 and IL-15:effect on viral transcriptional activation, cellular proliferation and endogenous cytokine production. J Clin Immunol, 1998;18:124–131.
Bayard-McNeeley M, Doo H, He S, Hafner A, et al. Differential effects of interleukin-12, interleukin 15, and interleukin 2 on human immunodeficiency virus type 1 replication in vitro. Clin Diag. Lab Immunol, 1996;3:547–553.
Shapiro L, Puren AJ, Barton HA, et al. Interleukin 18 stimulate HIV type 1 in monocytic cells. Proc. Natl Acad Sci USA, 1998;95:12550–12555.
Gendelman HE, Orenstein JM, Martin MA, et al. Efficient isolation and propagation of human immunodeficiency virus on recombinant colonystimulating factor 1-treated monocytes. J Exp. Med, 1988;167:1428–1441.
Folks TM, Justement J, Kinter A, et al. tCytokineinduced expression of HIV-1 in a chronically infected promonocyte cell line, Science, 1987; 238:800–802
Ho DD, Hartshorn KL, Rota TR, et al. Recombinant human interferon alpha-A suppresses HTLV-III interferon alpha-A suppresses HTLV-III replication in vitro. Lancet, 1985;I:1602–604.
Poli G, Orenstein JM, Kinter A, et al. Interferonalpha but not AZT suppresses HIV expression in chronically infected cell lines. Science, 1989;244:575–577.
Shirazi Y, Pitha PM. Interferon alpha-mediated inhibition of human immunodeficiency virus type 1 provirus synthesis in T-cells. Virology, 1993;193:303–312.
Maciaszek JW, Parada NA, Cruikshank WW, et al. IL-16 represses HIV-1 promoter activity. J. Immunol, 1997;158:5–8.
Scala E, D’Offizi G, Rossi R, Tirriziani O, et al. C-C chemokines, IL-16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection. J Immunol, 1997;158:4485–4492.
Schuitemaker H, Kootstra NA, Koppelman MH, et al. Proliferation-depended HIV-1 infection of monocytes occurs during differentiation into macrophages. J. Clin Invest, 1992;89:1154–1160.
Kazazi F, Mathijs JM, Chang J, et al. Recombinant interleukin 4 stimulated human immunodeficiency virus production by infected monocytes and macrophages. J Gen Virol, 1992;73:941–949.
Foli A, Saville MW, Baseler MW, Yarchoan R. Effects of the Th1 and Th2 stimulatory cytokines interleukin 12 and interleukin 4 on human immunodeficiency virus replication. Blood, 1995;85:2114–2123.
Weissman D, Poli G, Fauci AS. IL-10 synergizes with multiple cytokines in enhancing HIV production in cells of monocytic lineage. J Acquir. Immune Defic Syndr Hum Retrovirol, 1995;9442–9449.
Akridge RE, Reed SG. Interleukin-12 decreases human immunodeficiency virus type 1 replication in human macrophage cultures reconstituted with autologous peripheral blood mononuclear cells. J. Infect Dis, 1996;173:559–564.
Poli G, Kinter AL, Justement JS, et al. Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells on the monocyte/macrophage lineage. J Exp Med, 1991;173:559–564.
Poli G, Kinter AL, Justement JS, et al. Retinoic acid mimics transforming growth factor beta in the regulation of human immunodeficiency virus expression in monocytic cells. Proc Natl Acad Sci. USA 1992; 89:2689–2693.
Biswas P, Poli G, Kinter AL, et al. Interferon gamma induces the expression of human immunodeficiency virus in persistently infected promonocytic cells (Ul) and redirects the production of virions to intracytoplasmic vacuoles in phorbol myristate acetate-differentiated Ul cells. J Exp Med, 1992;176:739–750.
Vicenzi E, Biswas P, Mengozzi M, Poli G. Role of proinflammatory cytokines and beta chemokines in controlling HIV replication. J Leukoc Biol, 1997;62:34–40.
Diagbouga S, Albert D, Fumoux F, et al. Relationship between IL-5 production and variations in eosino-phil during HIV infection in West Africa: influence of Mycobacterium tuberculosis infection. Scand J Immunol, 1999;49:203–209.
Dimitrov DS. How do viruses enter cells? The HIV coreceptors teach us a lesson of complexity. Cell, 1997;91:721–730.
Litman DR. Chemokine receptors — keys to AIDS pathogenesis. Cell, 1998;93:677–680.
Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: Function cDNA cloning of a seven-transmembrane G-protein-coupled receptor. Science, 1996;272:872–877.
Deng HK, Liu W, Ellmeier S, et al. Identification of a major co-receptor for primary isolates of HIV-1 Nature, 1996;381:661–666.
Dragic T. HIV-1 entry into CD+ cells is mediated by the chemokine receptor CC-CKR-5. Nature, 1996;381:667–673.
Alkahatib G, Combadiere C, Broder CC, et al. CCCK5: A RANTES, MIP-1, MPI-1 receptor as a fusion cofactor for macrophage-tropic HIV-1. Science, 1996;272:1955–1958.
Choc H, Farzan M, Sun Y, et al. The Betachemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell, 1996;85:1135–1148.
Doranz BJ, Rucker J, Yi Y, et al. A dual-tropic primary HIV-1 isolate that uses fusin and the betachemokine receptos CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell, 1996;85:1149–1158.
Cocchi F, DeVico AL, Garzine-Demo A, et al. Identification of RANTES, MPI-1 alpha and MIPbeta as the major HIV-suppressive factors produced by CD8+ T cells. Science, 1995;270:1811–1815.
Bleul C, Farzan M, Choe H, et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature, 1996;382:829–833.
Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature, 1996;382:635–638.
He J, Chen Y, Farzan M, et al. CCR3 and CCR5 are coreceptors for HIV-1 infection of microglia. Nature, 1997;385:645–649.
Poli G. Cytokines and the human immunodeficiency virus:from bench to bedside. Europ J Clin. Invest, 1999;29:723–732.
Zhang P, Huang Y, He T, et al. HIV-1 subtype and second-receptor use. Nature, 1996;383:768.
Tscherning C, Alaeus A, Fredriksson R, et al. Difference in chemokine coreceptor usage between genetic subtypes of HIV-1. Virol, 1998;241:181–189.
Bjorndal A, Sonnerborg A, Tscherning C, et al. Phenotypic characteristics of human immunodeficiency type 1 subtype C isolates from Ethiopian AIDS patients. AIDS Res Human Retro, 1999;15:647–653.
Ping L-H, Nelson JAE, Hoffman F, et al. Characterization of V3 sequence heterogeneity in subtype C human immunodeficiency virus type 1 isolates from Malawi: underrepresentation of X4 variants. J Virol, 1999;73:6271–628.
Milich L, Margolin BH, Swanstrom. Patterns of aminoacid variability in NSI-like and Si-like V3 sequences and a linked change in the CD4-binding domain of the HIV-1 entry Env protein. Virol, 1997;239:108–118.
Chesebro MW, Wehrly K, Nishio J, et al. Mapping of independent V3 envelope determinants of human immunodeficiency virus type 1 macrophage tropism and syncytium formation in lymphocytes. J Virol, 1996;7:9055–9059.
Tien PC, Chiu T, Latif A, et al. Primary subtype C HIV-1 infection in Harare, Zimbabwe. J Acquir. Immune Def Synd Human Retrovirol, 1999;20:147–153.
Balachandran R, Thampatty P, Enrico A, et al. Human immunodeficiency virus isolates from asymptomatic homosexual men and from AIDS patients have distinct biologic and genetic properties. Virol, 1991;180:229–238.
Tersmette M de Goede REY, Al BJM, et al. Differential syncytium-inducing capacity of human immune-deficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol, 1988;62:2026–2032.
Koot M, Keet IPM, Vos AHV, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD+ cell depletion and Progression of AIDS. Ann Intern Med, 1993;118:681–688.
Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science, 1996;273:1856–1862.
Morawetz RA, Rizzardi GP, Glauser D, et al. Genetic polymophism of CCR5 gene and HIV disease: the heterozygous (CCR5/Dccr5) genotype is neither essential nor sufficient for protection against disease progression. Europ J Immunol, 1997;3223–3227.
Kostrikis LG, Huang Y, Moore JP, et al. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med, 1998;4:350–353.
Lee B, Doranz BJ, Rana S, et al. Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4. J Virol, 1998;72:7450–7458.
van Rij RP, de Roda Husman AM, Brouwer M. Role of CCR2 genotype in the clinical course of synctium-inducing (SI) or non-SI human immunodeficiency virus type 1 infection and in the time to conversion to SI virus variants. J Infect. Dis, 1998;178:1806–1811.
Michael NL, Louie LG, Rohrbauch AL, et al. The role of CCR5 and CCR2 polymorphism in HIV-1 transmission and disease progression. Nat. Medicine, 1997;3:1160–1162.
Brambila A, Villa C, Rizzardi GP, et al. Shorter survival of SDFI-3’A/3’A homozygotes linked to CD4+ T cell decrease in advanced human immunodeficiency virus type 1 infection. J Infect Dis, 2000; 182:311–315.
Fowke KR, Dong T, Rowland-Jones SL, et al. HIV-1 resistance in Kenyan sex workers is not associated with altered cellular susceptibility to HIV-1 infection or enhanced β-chemokine production. AIDS Res Hum Retroviruses, 1998;14:1521–1530.
Anzala AO, Ball TB, Roston T, et al. CCR2-641 allele and genotype association with delayed AIDS progression in African women. University of Nairobi Collaboration for HIV Research. Lancet, 1998;102:1758–1765.
Brander C, Walker BD. T lymphocytes responses in HIV-1 infection: implications for vaccine development. Current Opin Immunol, 1999;11:451–549.
Goulder PJR, Brander C, Annamalai K, et al. Differential Narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and Caucasoid Adults and children. J Virol, 2000;74:5679–5690.
Rowland-Jones S, Sutton J, Ariyoshi K, et al. HIV-1 specific cytotoxic T cells in HIV-exposed but uninfected Gambian women. Nat Med, 1995;1:59–64.
Cao H, Mani I, Vincet R, et al. Cellular immunity to human immunodeficiency virus type (HIV-1) clades: relevance to HIV-1 vaccine trials in Uganda. J Infect Dis, 2000;182:1350–1356.
Ahmed AT, Blose DA. Delayed type hypersensitivity skin testing. A review. Arch Derm, 1983;199:934–945.
Blatt SP Hendrix CW, Butzin CA, et al. Delayedtype hypersensitivity skin testing predicts progression to AIDS in HIV infected patients. Ann Int. Med, 1993;119:185–193.
Dolan MJ, Clerici M, Blatt SP, et al. In vitro T cell function, delayed type hypersensitivity skin testing and CD4 T cell subset phenotyping independently predict survival time in patients infected with HIV. J Infect Dis, 1995;172:79–87.
French MAH, Cameron PU, Grimsley G, Smith LA, Dawkins RL. Correction of human immunodeficiency virus-associated depression of delayedtype hypersensitivity (DTH) after zidovudine therapy: DTH, CD4+ T cell numbers, and epidermal Langerhans cell density are independent variables. Clin Immunopathol 1990;55:86–96.
Brown AE, Markowitz L, Nitayaphan S. DTH responsiveness of HIV-infected Thai adults. J Med. Assoc Thai, 2000;83:633–639.
Klein RS, Sobel J, Flanigan T, Smith D, Margolick JB. Stability of cutaneous anergy in women with or at risk for HIV infection. HIV Epidemiology Research Study Group. J Acquir Immune Defic. SyndrHum Retrovirol, 1999;20:238–244.
Miller WC, Thielman NM, Swai N, et al. Delayed type hypersensitivity testing in Tanzanian adults with HIV infection. J Acquir Immune Defic Syndr. Hum Retrovirol, 1996;12:303–308.
Fine PEM, Sterne JA, Penninghaus JM, et al. Delayed-type hypersensitivity, mycobacterial vaccines and protective immunity. Lancet, 1994; 3344:1245–1249.
Selwyn PA, Sckell BM, Alcabes P, et al. High risk of tuberculosis in HIV-infected drug users with cutaneous anergy. JAMA, 1992;268:504–509.
Elliot AM, Hurst TJ, Balyeku MN, et al. Immune response to Mycobacterium tuberculosis in HIV-infected and uninfected adults in Uganda: application of a whole blood cytokine assay in an epidemeological study. Int J Tuberc Lung Dis, 1998;239–246.
Kaslow RA, Carrington MN, Apple R, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med, 1996;2:405–410.
Carrington M, Nelson GW, Martin MP, et al. HLA and HIV-1: Heterozygote advantage and B*35-Cw*04 disadvantage. Science, 1999;283:1748–1752.
Ireneus P, Keet M, Tang J, et al. Consistent associations of HLA class I and II and transporter gene products with progression of human immunodeficiency virus type infection in homosexual men. J. Infect Dis, 1999;188:299–309.
MacDonald KS, Fowke KR, Kimani J, et al. Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type I infection. J Infect Dis, 2000; 181:1581–1589.
Puren AJ, Ramjee G, Abdool-Karim S, Gray CM. HLA association with HIV-1 seronegative sex workers from KwaZulu-Natal, South Africa. In Program and abstracts of the XIII International Conference on AIDS; July 9–14, 2000, Durban, South Africa.
Clerici M, Shearer GM. The Th1-Th2 hypothesis of HIV infection: new insights. Immunol Today, 1994;15:575–581.
Hyjiek E, Lischner HW, Hyslop T. Cytokine patterns during progression to AIDS in children with perinatal HIV infection. J Immunol 1995; 155:4060–4071.
Maggi E, Mazzeti M, Ravina A, Annunziato F, de Carli M, Piccinni MP, et al. Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0. Science, 1994;265:244–248.
Meyaard L, Otto SA, Keet PM, et al. Changes in cytokine secretion patterns of CD4+ T cell clones in human immunodeficiency virus infection. Blood, 1994;12:4265–4268.
Maizels RM, Bundy DA, Selkirk ME, et al. Immune-logical modulation and evasion by helminth parasites in human population. Nature, 1993;365:797–805.
Pearlman E, Kazura F, Hazlet F, Boom W. Modulation of murine cytokine responses to mycobacterium antigens by helminth-induced T helper 2 cell
Bentwich Z, Maartens G, Torten D, et al. Concurrent infections and HIV pathogenesis. AIDS, 2000; 14:2071–2081.
Wodarz D, Nowak MA. CD8 memory, immunodominance, and antigenic escape. Eur J Immunol, 2000;30:2704–2712.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Kluwer Academic Publishers
About this chapter
Cite this chapter
Zijenah, L.S., Katzenstein, D.A. (2002). Immunopathogenesis of AIDS. In: Essex, M., Mboup, S., Kanki, P.J., Marlink, R.G., Tlou, S.D., Holme, M. (eds) AIDS in Africa. Springer, Boston, MA. https://doi.org/10.1007/0-306-47817-X_3
Download citation
DOI: https://doi.org/10.1007/0-306-47817-X_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-46699-1
Online ISBN: 978-0-306-47817-8
eBook Packages: Springer Book Archive