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Objective: To determine whether the anti-angiogenesis agent DS-4152 inhibits the replication of HIV-1 in vitro., Design: A sulfated polysaccharide-peptidoglycan DS-4152 has recently been identified as a potent and selective inhibitor of Kaposi's sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of DS-4152 alone and in combination with dideoxynucleosides., Methods: Activity of DS-4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood lymphocyte cells. The inhibitory effect of the compound on syncytium-formation was determined by cocultivation of Molt-4 cells with Molt-4/IIIB cells. Inhibition of virus adsorption to the host cells was measured by a p24 antigen capture enzyme-linked immunosorbent assay., Results: DS-4152 showed potent and selective inhibition of HIV-1 replication in the cell systems. Its 50% effective concentration for HIV-1 (IIIB strain) in MT-4 cells was 0.7 microgram/ml. The compound was not cytotoxic at concentrations < or = 100 micrograms/ml. DS-4125 proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1 activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by the presence of DS-4152., Conclusion: DS-4152 has the potential, from these in vitro studies, to function as an anti-HIV-1 as well as an anti-angiogenesis agent. In order to determine this possibility, consequences of DS-4152 infusion on HIV-1 p24 serum levels and CD4+ cell counts over time are being examined in ongoing clinical trials in the United States on patients with AIDS-associated KS.

Objective: To determine circulating viral load in HIV-2-infected individuals., Methods: Viral load was determined in 40 HIV-2-infected adults using standardized quantitative cell and qualitative plasma viraemia assays. We also tested for proviral HIV-2 DNA using single and nested polymerase chain reaction (PCR) in fresh lymphocytes from 27 subjects. The results were compared, on the basis of the CD4+ lymphocyte count, with our published data for HIV-1 infection., Results: HIV-2 was isolated from peripheral blood mononuclear cells (PBMC) from 19 individuals and plasma from four patients. The rate of cell and plasma viraemia positivity correlated with the CD4+ cell count and HIV-2 virus load increased as the CD4+ cell count fell. The cellular HIV-2 load in the patients with a CD4+ count < 200 x 10(6)/l was similar to reported values for HIV-1, but the HIV-2 isolation rate from the plasma of these individuals was significantly lower than for HIV-1. When the CD4+ count was between 200 and 500 x 10(6)/l, the rate of HIV-2 isolation from plasma and the cellular virus load were both significantly lower than for HIV-1. When the CD4+ count was > 500 x 10(6)/l, HIV-1 and HIV-2 were undetectable in plasma and HIV-1 was isolated from PBMC in significantly more cases than HIV-2. By single PCR, amplification were positive in 14 out of 27 subjects and there was a correlation between positivity and CD4+ cell count. By nested PCR, only four of the 27 subjects, all with a high CD4+ count, remained negative., Conclusions: Differences in viral load between individuals infected with HIV-2 and those infected with HIV-1 could partly account for reported differences in the pathogenicity of the two viruses.

Objective: To characterize the biological properties of HIV isolates obtained at the time of primary infection, and relate this to the subsequent course of the infection., Methods: Syncytium-inducing (SI) capacity, tropism for cell lines (MT4 and H9) and replication rate were determined in 49 HIV isolates obtained from 17 HIV seroconverters. Thirteen of the 17 patients had a symptomatic primary HIV infection. Correlation between biological phenotype and clinical progression was analysed., Results: SI isolates were recovered in six patients from the first sample taken during primary infection, non-SI (NSI) isolates only were identified in 10 of the patients and isolation culture was negative in one patient. For all patients from whom SI virus was initially isolated, this phenotype persisted during the follow-up period (range, 17-219 weeks). The duration of fever during primary infection was longer for patients with SI isolates than for patients with NSI isolates (P = 0.05). Both types of isolates were associated with a significant fall in CD4 lymphocytes during follow-up (P < 0.05). Patients with SI isolates developed HIV-related immune deficiency more rapidly than patients with NSI isolates (P < 0.05)., Conclusions: The biological phenotype of HIV strains isolated during the time of seroconversion may be an important determinant of the subsequent course of the infection.

Chronic infection of the T-lymphocyte cell line JM with HIV-1 isolate GB8 results in the formation of multinucleate cells (syncytia). Transmission electron microscopy of these syncytia showed the presence of HIV particles both at the cell surface and within cytoplasmic vesicles. HIV particles were observed in dilated Golgi cisternae and Golgi-derived vesicles and in large vacuoles near the periphery of the syncytia. Immunolabelling was performed using an affinity-purified antiserum to the Golgi enzyme galactosyltransferase. This enzyme was consistently localized within both the Golgi apparatus and within virus-containing vesicles of JM syncytia, indicating that these vesicles originated from the Golgi apparatus.

An antigen-specific feline T-lymphocyte cell line (Q201) was generated and infected in vitro with the feline immunodeficiency virus (FIV). Syncytium formation and the release of the viral core protein p24 into culture fluid were accompanied by a reduction in expression of the CD4 surface antigen. The reduction in CD4 expression was transient, the resulting persistently infected population of cells expressing levels of CD4 comparable to those observed prior to infection. Persistently infected cells gradually lost expression of major histocompatibility antigen (MHC) class II while maintaining pre-infection levels of expression of CD4, MHC class I, CD18 or CD29.