Host cell factors act together with regulatory genes of the human immunodeficiency virus (HIV) to control virus production. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV gene expression. DNA transfection experiments showed that 4 of 18 clones had high levels of HIV gene expression measured by both extracellular virus production and transactivation of the HIV long terminal repeat in the presence of the trans-activator (tat) gene. Karyotype analyses revealed a 94% concordance (17/18) between human chromosome 12 and HIV gene expression. Other chromosomes had an 11 to 72% concordance with virus production.

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Alternative strategies for vaccination against influenza that elicit both systemic antibody and mucosal IgA responses are needed to improve the efficacy in protection against infection. This study demonstrated that oral delivery of inactivated influenza vaccine with the heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli elicited the spectrum of humoral and cell-mediated responses in BALB/c mice critical for the protection and recovery from influenza virus infection. Coadministration of LT with oral influenza vaccine increased antiviral serum IgG and mucosal IgA responses compared with administration of oral influenza vaccine alone. Serum hemagglutination-inhibition and neutralizing antibodies were also augmented by LT. The adjuvant potentiated protection from infection with influenza A H3N2 viruses in mouse lower and upper respiratory tracts, enabling the use of lower doses of oral vaccine. Coadministration of LT with oral inactivated influenza vaccine induced influenza virus-specific proliferative T cells, interleukin-2 production, and major histocompatibility complex class I-restricted cytotoxic T cells.

The trans-activator response region (TAR) RNA in the human immunodeficiency virus type 1 (HIV-1) and HIV-2 long terminal repeat forms stem-loop secondary structures in which the loop sequence is essential for trans activation. We investigated how the HIV trans-activation mechanism encoded on human chromosome 12 relates to the TAR RNA loop-dependent pathway. DNA transfection experiments showed that trans activation in human-hamster hybrid cells with the single human chromosome 12 and human T-cell lines was highly dependent on the native sequences of the HIV-1 TAR loop and the HIV-2 5' TAR loop. In nonhuman cell lines or hybrid cells without chromosome 12 that supported trans activation, the cellular mechanism was independent of the HIV-1 TAR loop and the response to mutations in the HIV-2 TAR loops differed from that found in human T-cell lines and human-hamster hybrid cells with chromosome 12. Our results suggest that the human chromosome 12

SUMMARYRNA I* (see end of Summary) of a cold-adapted and temperature-sensitive (ts) influenza virus mutant A/Ann Arbor/6/6o has a different mobility from RNA I of wild-type (wt) A/Ann Arbor/6/6o when subjected to electrophoresis through acrylamide/agarose gels in the absence of denaturing agents. Detection of this lesion in RNA I of the mutant virus was dependent on the temperature of the gel during electrophoresis. Because RNA t is believed to code for a protein involved in virus-specific RNA synthesis we compared phenotypes of virion transcriptases in the wt and mutant viruses. The enzyme of the mutant virus was found to be about 4o~ less active at 40 °C than the enzyme of the wt virus when related to their activities at 31 °C. Two cold-adapted ts recombinants which derive their RNA l from the mutant A/Ann Arbor{6[6o have virion transcriptases with a phenotype similar to that of their mutant parent. Three different cold-adapted ts recombinants, however, which also derive their RNA t from the mutant A/Ann Arbor/6/6o, have virion transcriptases with a phenotype similar to that of wt virus. We conclude, therefore, that the conditional-lethal ts property of A/Ann Arbor/6/6o mutant and its recombinants is independent of the phenotypic marker observed for the A/Ann Arbor/6/6o mutant virion transcriptase, and that the lesion in RNA I of the mutant may also be unrelated to the observed difference between virion transcriptases of the mutant and wt A/Ann Arbor[6/6o viruses.The phenotypes of the virion transcriptases in recombinants did, however, correlate with the derivation of their RNA z. This suggests that the increased temperature-sensitivity of virion transcriptase of the A/Ann Arbor/6/6o mutant is caused by either (0 a lesion (not necessarily conditionally lethal)that occurred in its RNA 2 during the course of cold-adaptation, or (z) a lesion in another gene whose product is a component of the virion transcriptase complex, but which lesion is only expressed phenotypically when there is a synergistic interaction in the transcriptase complex with the product of A/Ann Arbor/6/6o RNA 2.