Phenotypic characteristics of human immunodeficiency virus type 1 subtype C isolates of Ethiopian AIDS patients.

It has been estimated that, to date, about 48% of all HIV-infected people in the world carry HIV-1 subtype C virus. Therefore, it is of great importance to gain better knowledge about the genetic and biological characteristics of this virus subtype. In the present study, the biological properties of HIV-1 isolates obtained from nine Ethiopian patients with AIDS were studied. DNA sequencing of the V3 loop of gp120 classified the isolates as subtype C. In primary isolation cultures, virus infection was accompanied by syncytium formation and cell lysis. Interestingly, when examining the growth in primary monocyte-macrophage cultures, initial low-level virus replication was followed by a nonproductive state, from which virus could be rescued by cocultivation with Jurkat(tat) cells. Furthermore, none of the isolates replicated in T cell lines (CEM, MT-2, HuT-78, and H9) or in the promonocytic cell line U937 clone 2. All isolates could use CCR5 as coreceptor, whereas no isolates could use CCR2b, CCR3, CCR5, CXCR4, Bonzo/STRL33, or BOB/GPR15. The genotype of the V3 region correlated with the MT-2 negative/non-syncytium-inducing (NSI) phenotype. Comparative studies revealed that the scarcity of CXCR4 usage as well as other phenotypic characteristics of subtype C isolates distinguish this subtype. On the basis of these data, we suggest that in addition, factors other than viral phenotype may govern the pathogenic potential of subtype C isolates.

Differences in chemokine coreceptor usage between genetic subtypes of HIV-1.

HIV-1 uses chemokine coreceptors for cell entry. CXCR4 is the major coreceptor for T-cell-line-adapted isolates and CCR5 for non-T-cell-line-adapted isolates. This study investigated if coreceptor usage differs between genetic subtypes of HIV-1. Eighty-one primary isolates representing nine different genetic subtypes (A-J, except I) were tested on U87.CD4 glioma cells stably expressing chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4. Coreceptor usage was compared to biological phenotype of the isolates (rapid/high, syncytium-inducing or slow/low, non-syncytium-inducing) and to clinical and immunological status of the study subjects. CXCR4 usage was perfectly correlated to the biological phenotype for all subtypes; all of 26 isolates with rapid/high phenotype and none of 55 isolates with slow/low phenotype could infect the CXCR4 expressing cell line. Importantly, the CXCR4-positive, rapid/high phenotype was underrepresented among subtype C isolates. Furthermore, dual tropism for CXCR4 and CCR5 was not found among subtype D isolates. Uni- and multivariate analyses indicated that these subtype-specific differences in coreceptor usage were not due to differences in clinical status, CD4 counts, or treatment. This study shows that CXCR4 usage determines the biological phenotype for all subtypes, but that there appear to exist subtype-dependent differences in frequency of usage of certain coreceptors. This opens up the possibility that genetic subtypes may differ in important biological properties such as virulence, tissue tropism, and transmissibility.

Insights into the mechanisms of vertical transmission of HIV-1. BIOMED2 Working Group on the in utero transmission of HIV-1.

This paper is a summary of three oral presentations, as well as the ensuing discussion, at the Rijeka/Opatija 3rd Alps Adria Immunology meeting by three members of the European Biomed group on vertical transmission of HIV (G. Chaouat, F. Barre-Sinoussi, G. Scarlatti). This group also involves the laboratories of D. Dormont (CEA, Fontenay aux roses, France), P. Gounon (Electron Microscopy, the Pasteur Institute, France; Irène Athanassakis, University of Crete, Greece; Eva Maria Fenyö, Karolinska Institute, Sweden; and Larry Guilbert, Canada). As such, this paper intends to be neither a review, nor an original article, but rather is an opinion paper discussing the working hypothesis of this network, as well as some of their recent results, which were presented at this meeting. The paper was issued at the request of the organizers of the meeting.

Recurrent renal salt wasting in a child treated with carboplatin and etoposide.

BACKGROUND: Nephrotoxicity of carboplatin is rare, especially in children with normal renal function. A 3-year-old boy had localized esthesioneuroblastoma and received 2 courses of carboplatin (200 mg/m2/day during a 1-hour infusion for 3 consecutive days) associated with etoposide (150 mg/m2/day after carboplatin). Because of a good tumor response, a second course was given 21 days later. Complete surgical excision and local irradiation were performed. However, the tumor recurred a few months later, and the patient subsequently died of the disease. METHODS: Renal function initially was assessed by standard baseline chemistry and technetium-panetetic acid (Tc-DTPA) clearance. Follow-up included ionic controls and tubular exploration during the episodes of hyponatremia. RESULTS: Hyponatremia occurred 4 days after completion of the first course and resolved after intravenous supplementation. It recurred 20 days after the second course despite salt and magnesium prehydration and posthydration and resolved 17 days later. No glomerular dysfunction was noticed. The association of urinary bicarbonate loss with elevated N-acetyl-beta-glucosaminidase suggested a proximal tubular damage. CONCLUSIONS: Standard doses of carboplatin may lead to recurrent renal salt wasting in children with initially normal renal function.