Although natural mumps virus infection is believed to induce lifelong immunity, our laboratory was confronted with 82 patients who developed mumps-evoking lesions but exhibited serological evidence of a booster immune response, namely a rise or a high titer of virus-specific IgG, without IgM. In order to provide arguments favoring the existence of recurrent mumps attacks, the age, symptomatology, and humoral response of these patients (group 1) were compared to that of 82 randomly selected true primary infected patients (group 2), 10 parainfluenza virus-infected patients (group 3), and 20 noninfected mumps-immune subjects (group 4). Enzyme-linked immunosorbent assay (ELISA) procedures with different viral antigenic preparations were used for determination of specific IgM, IgA, IgG, IgG subclasses, and IgG avidity. The patients of group 1, older than those of group 2 (28 vs. 10 years, P < 0.0001), presented a significantly less severe and less typical symptomatology. Against the whole virus they exhibited IgG of higher avidity (P < 0.001), a lower prevalence and titer of IgA (10 vs. 68%, P < 0.0001 and 278 vs. 5,009, P < 0.001, respectively). Values obtained for IgG 1, 2, and 3 were significantly different between the two groups. Prevalence and absorbance of nucleocapsid-directed IgG 3 were significantly lower in group 1 (27 vs. 46%, P < 0.01 and 0.444 vs. 0.869, P < 0.01, respectively). A significant discrepancy also allowed patients from group 1 to be distinguished from those of groups 3 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

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Chimeric primate lentiviruses composed of SIV and HIV genes may allow the analysis of the role of these discrete HIV genes in viral pathogenesis in macaque monkeys. We have constructed a chimeric virus in which the env, rev, tat, and vpu genes of HIV-1 Lai replace the env, rev, and tat genes of the SIVmac239 genome. This virus, SHIVsbg, replicates efficiently in rhesus (Indian and Chinese subspecies) and cynomolgus monkeys with viral loads in PBMC and lymph nodes of up to one infected cell per 30 cells during the acute phase of the infection. Sera from all monkeys recognize specific HIV-1 glycoproteins. The onset of lymphadenopathy in all animals was concurrent with a depletion of CD4 lymphocytes in peripheral blood. The virulence of this SHIV for rhesus and cynomolgus monkeys therefore closely parallels that of HIV-1 for human in the acute phase of the infection. Changes in the env and vpu genes of a molecular clone of HIV-1 can now be analyzed after passage in nonhuman primate species as the SHIVsbg replicates efficiently. The SHIVsbg-macaque model is an important step in the development of a readily available animal model for HIV-1 vaccine studies.

Anti-hepatitis B virus (HBV) therapy leads to the emergence of mutant viral strains during the treatment of chronic hepatitis B with nucleos(t)ides analogues. The existence of HBV variants with primary antiviral resistance may be important for treatment choice. We studied two patients with chronic HBV infection by sequencing the HBV polymerase gene. They had adefovir-and tenofovir-related mutations in the viral polymerase, although they had never been treated. These mutations were rtV214A/rtN238T in one patient and rtA194T in the other. Thus, mutations in untreated patients deserve cautious surveillance. These data indicate that mutations that can theoretically confer adefovir or tenofovir resistance may emerge in treatmentnaive patients.

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The infection of macaque monkeys by attenuated simian immunodeficiency virus can vaccinate against pathogenic molecular clones and isolates of the same virus. The correlates of this potent protective immunity are not fully understood but may be the key to an effective AIDS vaccine for humans. Aiming to determine whether host immune responses to envelope glycoprotein are an essential component of the immunity to primate lentiviruses, we have tried to superinfect SIVmac-infected macaque monkeys with SHIVsbg, a chimeric primate lentivirus constructed from the SIVmac239 genome with the env, rev, tat, and vpu genes from HIV-1 Lai. After inoculation of a large dose of SHIVsbg, the chimeric virus was isolated by coculture of mononuclear blood cells from four of five SIV-infected monkeys, but three animals were protected from extracellular SHIV viremia and did not seroconvert to HIV-1 glycoproteins. In the two SIV-infected monkeys that did develop SHIV viremia, cell-associated viral load was reduced at least 100-fold. These data indicate that an antiviral response capable of effectively controlling primate lentivirus replication might not necessarily involve the envelope glycoprotein.

The poor response to the combined antiviral therapy of pegylated alfa-interferon and ribavarin for hepatitis C virus (HCV) infection may be linked to mutations in the viral envelope gene E1E2 (env), which can result in escape from the immune response and higher efficacy of viral entry. Mutations that result in failure of therapy most likely require compensatory mutations to achieve sufficient change in envelope structure and function. Compensatory mutations were investigated by determining positions in the E1E2 gene where amino acids (aa) covaried across groups of individuals. We assessed networks of covarying positions in E1E2 sequences that differentiated sustained virological response (SVR) from non-response (NR) in 43 genotype 1a (17 SVR), and 49 genotype 1b (25 SVR) chronically HCV-infected individuals. Binary integer programming over covariance networks was used to extract aa combinations that differed between response groups. Genotype 1a E1E2 sequences exhibited higher degrees of covariance and clustered into 3 main groups while 1b sequences exhibited no clustering. Between 5 and 9 aa pairs were required to separate SVR from NR in each genotype. aa in hypervariable region 1 were 6 times more likely than chance to occur in the optimal networks. The pair 531–626 (EI) appeared frequently in the optimal networks and was present in 6 of 9 NR in one of the 1a clusters. The most frequent pairs representing SVR were 431–481 (EE), 500–522 (QA) in 1a, and 407–434 (AQ) in 1b. Optimal networks based on covarying aa pairs in HCV envelope can indicate features that are associated with failure or success to antiviral therapy.

Each y a few cases of TBE infection are described in Alsace, France which lies at the occidental limit of the endemic zone of tick-borne encephalitis (TBE). Hence we carried out a retrospective epidemiological and clinical study of TBE infection in Alsace. Data were collected from serological results sent to the Institut de Virologie (Université Louis Pasteur) in Strasbourg. All samples positive for specific IgM against TBE were retained. The physician in charge of each patient was asked to provide clinical, epidemiological and biological data and with his agreement the medical file was referred to us. Since 1968, 64 cases of TBE infection, occurring between April and November, had been described. In 56% of cases, flu-like symptoms preceded neurological symptoms. Most patients had meningitis (54%) or meningoencephalitis (34%). There was no death due to TBE. Two areas were more highly endemic for the disease: the Guebwiller valley in low mountain country and the Neuhof forest, near Strasbourg in the plain of Alsace. In the last 2 y of the study, a third zone seemed to emerge, in the Munster valley. This epidemiological survey revealed the existence in Alsace of 2 endemic zones of TBE with a third zone possibly emerging in the last few y. The survey must be continued to follow the evolution of the disease.