Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

Human herpesvirus 8 and Epstein Barr-virus in a cutaneous B-cell lymphoma and a malignant cell line established from the blood of an AIDS patient.

Human Herpesvirus 8 (HHV-8) has been consistently associated with Primary Effusion Lymphoma (PEL or body-cavity-based lymphoma) but not with other lymphomas. This paper reports on an AIDS patient without obvious malignant effusion in body cavities but with a cutaneous lymphoma where HHV-8 and Epstein-Barr virus (EBV) were detected by PCR and electron microscopy. Both viruses were also detected in all the cells of a malignant cell line (BBG1) established from the patient's peripheral blood mononuclear cells. As in PEL and PEL-derived cell lines, both the tumor and the lines lacked B-antigen expression in immunological studies but were of the same B origin as shown by clonal immunoglobulin gene rearrangements. In contrast to other co-infected cell lines, BBG1 and subclones spontaneously expressed the HHV-8 lytic antigens p40, p27, p60 and the EBV transforming latent antigen EBNA2. These data suggest that the clinical and biological features of HHV-8-and EBV-associated lymphomas could be wider than has been described to date in PEL particularly with the in vivo presence of circulating malignant dually-infected cells engaged in a spontaneous HHV-8 lytic infection.

Transient infection of astrocytes with HIV-1 primary isolates derived from patients with and without AIDS dementia complex.

We have studied the replication capacity of primary HIV-1 isolates obtained from four AIDS patients in astrocytes. Two patients (P1 and P2) had neurological manifestations without AIDS Dementia Complex (ADC). The other two patients (P3 and P4) had ADC. Two astrocytoma cell lines and normal fetal astrocytes were inoculated with each of these four viral isolates. Viral DNA and mRNA synthesis and also protein accumulation were followed at various times after infection. We found that tumoral as well as fetal astrocytes were susceptible to HIV-1 infection. Three of four viral isolates (P2, P3, P4) were able to infect astrocytes. Both ADC viral isolates (P3, P4) infected astrocytes with identical transcriptional patterns: rev, nef and unspliced mRNAs were expressed for 2 days after infection. The non-ADC patient (P2) with the isolate leading to viral replication in astrocytes had an HIV-1 associated multifocal demyelinating neuropathy. In this case, only nef and unspliced mRNAs were detected a few days after virus inoculation. In all cases, infection of astrocytes was transient and the level of unspliced mRNAs in infected astrocytes was lower than in chronically HIV-1 infected T cells. More extensive work would allow a better understanding of the role of astrocytes in ADC.