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The C-terminal cytoplasmic tail of chemokine receptors is important for their internalization upon ligand binding. We generated several deletion mutants of the C-terminal cytoplasmic tail of CXCR-4, a co-receptor for T cell line tropic strains of human immunodeficiency virus type 1 (HIV-1), to know whether or not co-receptor internalization is associated with HIV-1 entry. Our data showed that the removal of C-terminal 15 amino acid residues of the cytoplasmic tail from CXCR-4 completely abolished its internalization, but did not affect the co-receptor activity at all. Co-receptor activity was fully retained even when all 45 amino acid residues in the C-terminal cytoplasmic tail had been deleted. These data indicated that no cytoplasmic tail nor internalization of CXCR-4 is required for its co-receptor activity for HIV-1 entry.

Factor Xa is a serine proteinase which functions principally at coagulation cascades. Factor Xa-like immunoreactivity has been examined in several human organs. Antibodies to the Factor stained macrophages in some tissues examined, including microglia in the brain white matter. They also stained epithelial cells in the nose, bronchus and duodenum. Some brainstem neurons, such as those in the oculomotor nucleus, substantia nigra and pontine nucleus, were also positive for the Factor. As reported by others, these results suggest that factor Xa may have pleiotrophic functions. Furthermore, the prefential localization to epithelium in the nose and bronchus is interesting in view of the previous notion that several viruses targeting the respiratory tract require factor Xa-like cellular proteinases for their replication and spread.

Interferon-beta (IFN-beta) strongly inhibited the expression of the hemagglutinin-neuraminidase (HN) gene of Newcastle disease virus (NDV), a paramyxovirus, in HeLa cells under the conditions where it did not affect the expression of the four upstream genes encoding the nucleocapsid protein, phosphoprotein, membrane protein and fusion protein. Even the downstream gene, encoding the large protein as well as the genome replication, appeared to be less susceptible to IFN-beta than the HN gene. This selective action of IFN-beta did not appear to be attributable to its well characterized antiviral mechanisms such as acceleration of RNA decay and translation inhibition. No similar down-regulation of a particular gene expression was found with another paramyxovirus, Sendai virus, or with a rhabdovirus, vesicular stomatitis virus, or seems to have been reported previously with any negative-strand RNA viruses. This new effect of IFN-beta thus suggests gene expression mechanism unique to NDV and may further lead to the discovery of a novel biochemical effect of IFN-beta.

Human macrophage inflammatory protein-1 alpha (MIP-1alpha) is a chemotactic cytokine, which binds to macrophages, T cells, and B cells affecting their activation. We found novel polymorphisms at four sites within MIP-1alpha gene in Japanese population: C to T in exon 2; A to G in intron 2; C to G and A to G in exon 3. They occurred on the same allele. Although MIP-1alpha effectively suppresses the replication of HIV-1 in vitro, we observed no statistically significant difference in the allele frequency of this polymorphism between HIV-1-infected and uninfected individuals in Japanese population. Since an increased transcription level of MIP-1alpha has been reported to be associated with inflammatory diseases such as atopic dermatitis, we also investigated the frequency of these polymorphisms among patients with atopic dermatitis, HIV-1-infected individuals (with a normal IgE level), and healthy donors. A small increase in ratio of homozygotes to other genotypes was observed in patients with atopic dermatitis (P = 0.04).

There was an epidemic of non-A non-B hepatitis in a small area of a town in the central part of Japan, which began with an outbreak of several patients in 1981 and then spread extensively with the result that about one third of the inhabitants showed abnormality in serum liver function tests at the health check performed in 1985. We determined histological diagnoses on that occasion for 167 individuals of the abnormal population and recently assayed antibodies against hepatitis C virus (HCV) for most of their sera left available. Histologically, chronic active hepatitis (CAH) was the major pattern, accounting for 59.3% (99 cases) of the total. Others were chronic persistent hepatitis (CPH) (13.2%), chronic lobular hepatitis (CLH) (16.2%), liver cirrhosis (LC) (6.6%) and fatty liver (4.8%). In the serological studies, the newly developed system to detect antibodies against the viral core protein p 22 was found to be much more sensitive than the conventional system to detect anti C 100-3 antibodies. By using these two methods in combination, we found that 82% were antibody-positive, indicating strong implication of HCV in this epidemic. This was further supported by direct detection of the viral genome in patients' sera by polymerase chain reaction following reverse transcription. We further found a strong correlation between the histological inflammatory activity and the antibody prevalence, since nearly all (97.6%) of the CAH cases were antibody-positive by at least either of the antibody assays, while only about 50% were positive in the less active cases such as CPH and CLH.

Most of the information on the structure, function and replication of paramyxoviruses has been obtained from studies on Newcastle disease virus (NDV), simian virus 5 (SV5), and Sendal virus (see reviews by Kingsbury, 1973; Choppin and Compans, 1975; Rott and Klenk, 1976). The virion consists of a helical ribonucleoprotein, the nucleocapsid, which is surrounded by an envelope (Fig.l). The nucleocapsid is composed of the single stranded RNA genome and a carbohydrate-free polypetide subunit, the NP protein. The envelope contains lipid which is derived from the plasma membrane of the host cell (Klenk and Choppin, 1969) and is present in the form of a bilayer (Landsberger et al., 1971). Associated with the outer side of the bilayer are spikes which are composed of glycoproteins (Klenk, et al., 1970; Chen, et al., 1971), the inner side is coated by the carbohydrate-free M protein. There are 2 types of spikes: one type consists of glycoprotein HN which has hemagglutinating and neuraminidase activity (Scheid et al., 1972; Scheid and Choppin, 1973; Seto et al., 1973;Tozawa, et al., 1973; Shimizu, et al., 1974), and the other one consists of glycoprotein F which induces cell fusion and hemolysis (Homma and Ohuchi, 1973; Scheid and Choppin, 1974; Seto, et al., 1974). It is generally agreed that these activities reflect the essential roles which both

Large plaque (G) and small plaque (8) variants were cloned from stock culture of Sindbis virus. Addition of protamine to agar overlay was shown to have little or no effect on the size of plaques produced by G variant, whereas S virus plaque size was significantly increased. This finding suggests that the S variant is more susceptible than the G variant to the inhibitory action of agar factor. The G and S variants differed markedly in their sensitivity to the antiviral action of interferon. Evidence was obtained that the S variant is more susceptible to the action of interferon. The difference of G and S variants in susceptibility to the action of interferon and agar factor may account for the difference of their plaque size. Growth and cytopathic effect of the S variant in a HVJ carrier HeLa cell culture (HeLaHVJ) was greatly enhanced in contrast to those in normal HeLa cells. Enhancement of growth of wild-type virus in HeLaHVJ cells was not so significant as in the case of the S variant. These observations were discussed in relations to the properties of the S variant and the cells of HeLaHVJ.