Human Immunodeficiency Virus Type 2 Infection Associated with AIDS in West Africa

Clavel, François; Kamal, Mehnaz; Chamaret, S.; Guétard, Denise; Favier, Véronique; Nina, Jaime; Santos-Ferreira, Marie-Odette; Champalimaud, J L; Montagnier, Luc

doi:10.1056/nejm198705073161903

Cited by 279 publications

(86 citation statements)

References 15 publications

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“…In HIV-2, disease progression is slower than in HIV-1, with limited impact on the survival of the majority of infected adults (12)(13)(14), although it apparently manifests the same clinical spectrum (15,16). Both horizontal and vertical HIV-2 transmission rates are much lower than for HIV-1 (17,18).…”

Section: H Uman Immunodeficiency Virus Type 1 Pathogenesis Is Generalmentioning

confidence: 99%

CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load

Sousa

Carneiro

Meier‐Schellersheim

et al. 2002

The Journal of Immunology

437

323

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The causal relationships among CD4 cell depletion, HIV replication, and immune activation are not well understood. HIV-2 infection, “nature’s experiment” with inherently attenuated HIV disease, provides additional insights into this issue. We report the finding that in HIV-2 and HIV-1 patients with a comparable degree of CD4 depletion the imbalance in the relative sizes of the naive and memory T cell populations and the up-regulation of CD4 and CD8 cell activation markers (HLA-DR, CD38, CD69, Fas molecules) are similar, even though the viral load in the plasma of HIV-2-infected patients is two orders of magnitude lower than in HIV-1 patients and HIV-2 patients are known to have slower rates of CD4 T cell decline and a better clinical prognosis. Moreover, we found a similar increase in the frequency of cycling CD4 T cells (Ki67+), which was in strong correlation with the expression of activation markers. Finally, the level of T cell anergy, as assessed by the proliferative responses to CD3 stimulation and to a panel of microbial Ags, proved to be comparable in HIV-1 and HIV-2 patients with a similar degree of CD4 depletion despite large differences in viral load. Our data are consistent with a direct causal relationship between immune activation and CD4 cell depletion in HIV disease and an only indirect relation of these parameters to the virus replication rate. Invoking the concept of proximal immune activation and virus transmission, which links efficient transmission of virus to local cell activation and proliferation in response to Ags and inflammation, we propose an integrative interpretation of the data and suggest that strongly elevated immune activation induces CD4 cell depletion and not vice versa, with potential implications for the choice of treatment strategies.

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Section: H Uman Immunodeficiency Virus Type 1 Pathogenesis Is Generalmentioning

confidence: 99%

CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load

Sousa

Carneiro

Meier‐Schellersheim

et al. 2002

The Journal of Immunology

437

323

View full text Add to dashboard Cite

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“…Cependant, il existe des réactions immunologiques croisées entre les protéines internes des deux sous-types de virus, conséquences d'épitopes communs entre chaque protéine codée par le gène gag [21]. 1 En revanche, les .…”

Section: B) Les Protéines Constitutives Des Virus Hivunclassified

Le SIDA

Barré‐Sinoussi¹,

Virelizier²

1989

bavf

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“…The human immunodeficiency virus (HIV) is the causative agent of the Acquired Immuno Deficiency Syndrome (AIDS) (Gallo and Montagnier, 1988). Soon after the discovery of HIV type 1 (HIV-1), a separate subtype, HIV type 2 (HIV-2), was identified in Western Africa (Clavel et a/., 1987). Both HIV subtypes can lead to AIDS, although the pathogenic course with HIV-2 might be longer.…”

Section: Introductionmentioning

confidence: 99%

Review

1996

Biological Chemistry Hoppe-Seyler

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Proteolytic enzymes have many physiological functions in plants, bacteria, viruses, protozoa and mammals. They play a role in processes such as food digestion, complement activation or blood coagulation. The action of proteolytic enzymes is biologically controlled by proteinase inhibitors and increasing attention is being paid to the physiological significance of these natural inhibitors in pathological processes. The reason for this growing interest is that uncontrolled proteolysis can lead to irreversible damage e.g. in chronic inflammation or tumor metastasis. This review focusses on the possible role of the cystatins, natural and specific inhibitors of the cysteine proteinases, in pathological processes. Key words: Cystatins / Cysteine proteinases / Inflammation / Inhibitors / Pathological processes. Cysteine ProteinasesCysteine Proteinases, synonymous with thiol proteinases, are small proteins with molecular masses varying from 23 to 24 kDa and with two catalytic residues, Cys25 and His159, which are involved in the hydrolytic reaction. Cysteine proteinases catalyze the hydrolysis of various polypeptide substrates and are most active under reducing and mildly acidic conditions (pH 5 -6.5). They have been detected in and isolated from a large number of biological sources including plants, bacteria, animals and humans. Bacterial cysteine proteinases are produced by Clostridium histolyticum, named clostripain, by hemolytic group A streptococci and by the pathogenic anaerobic Porphyromonas gingivalis, a bacterium associated with periodontitis. Bacterial cysteine proteinases probably play a role in the penetration of normal tissues by the bacteria and in the food digestion. Viral cysteine proteinases from picornaviruses, e.g. the poliovirus and rhinovirus type I, are involved in proteolytic cleavage of precursor proteins for virus replication and for the production of new virus particles. A virus-coded cysteine proteinase is involved in this process (Kay and Dunn, 1990; Körant et a/., 1985;. HIV-I also needs proteolytic processing by cysteine proteinases to regulate the expression of viral proteins (Guy ef a/., 1991). Protozoal cysteine proteinases are produced by a number of protozoan parasites to facilitate host invasion, metabolize host proteins, to degrade the host immune molecules or to use them for intracellular replication. Cysteine proteinases are produced by e.g. Trypanosoma cruzi, the causative agent of American trypanosomiasis or by Leishmania species, causing one of the six major parasitic diseases. Furthermore, human malarial parasites produce a broad scala of proteinases including cysteine proteinase which are involved in erythrocyte invasion and rupture (McKerrow, 1993). Mammalian cysteine proteinases are present in the lysosomes of cells. Lysosomes contain different cysteine proteinases, the most important being the cathepsins B, H, L and S Kirschke, 1981, Barrett et a/., 1988). These cathepsins have common ancestors and are related to papain. Cathepsin B has been detected in every tissue or cel...

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Human Immunodeficiency Virus Type 2 Infection Associated with AIDS in West Africa

Cited by 279 publications

References 15 publications

CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load

CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load

Le SIDA

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