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M Hayami

Publications and source records attributed to M Hayami.

At least 55 records · Page 3Linked to original sources
PubMed1999

A new genotype of TT virus (TTV) infection among Colombian native Indians.

Serum TTV DNA was assayed in 140 native Indians and 40 members of the general population in Colombia to determine the prevalence of TT virus (TTV) infection among Colombian native Indians. Of the 140 native Indians, 23 (16.4%) were positive for TTV DNA, compared to 4 (10.0%) of 40 from the general population (P = not significant). The prevalence of TTV DNA among native Indians was much higher than that of HBsAg and anti-HCV. Comparison of subjects with and without TTV DNA revealed no significant differences in all characteristics between the two groups. A phylogenetic tree, using the open reading frame 1 sequence (222 bp), indicated that the virus could be classified into four different genotypes, including three previously reported ones. The results show that TTV infection is common in Colombian native Indians without liver disease and also indicate the existence of a novel genotype of TTV.

Adolescent↗
PubMed1999

Genetic diversity of HIV-1 group M from Cameroon and Republic of Congo.

We analyzed 57 HIV-1 isolates from Cameroon and the Republic of Congo, with respect to the env C2V3 and/or the pol integrase regions. The results indicated that the topology of the pol tree correlated well with that of the env tree for four clusters of subtype D, F G and H, suggesting that these trees reflect the true evolution of the overall genome structures of these subtypes. However, of 22 Cameroonian isolates that were classified as subtype A based on env, 20 of them diverged in their pol sequence into two lineages that were completely different from the prototypical subtype A, tentatively designated as subtypes A1 and A2. The subtype A1 isolates (6 out of 22) were related in their env C2V3 regions with prototypical subtype A strain, but in their pol regions, they formed an independent cluster that diverged from known HIV-1 subtypes so far reported (except for subtypes I and J). The subtype A2 isolates (14 out of 22), which represent the major epidemic type of HIV-1 in Cameroon, clustered distinctly in both the env and pol trees with the recently described A/G mosaic strains from Nigeria and Djibouti. These two lineages were not spreading in the neighboring Republic of Congo.

Amino Acid Sequence↗
PubMed1999

Seroprevalence of hepatitis B virus, hepatitis C virus and GB virus-C infections in Siberia.

We studied the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus-C (GBV-C) infections in 348 Siberian natives who lived in the Kamchatka Peninsula of Russia. Of 348 samples studied, the seroprevalence of HBsAg and anti-HBs were 11.8% (41 of 348 samples) and 35.9% (125 of 348 samples), respectively. The prevalence of HCV infection was 1.4% (5 of 348 samples), and that of GBV-C RNA, using RT-PCR methods, was 7.5% (26 of 348 samples). In Siberia, the prevalences of HBV and GBV-C infections were about tenfold higher than those in Japan. The prevalence of HBsAg in subjects under 50 years of age was significantly higher than that in those over 50 years old (P < 0.05). Because HBV infection is highly endemic in Siberia, we propose that the community-based mass immunization must be conducted as soon as possible in this area.

Adolescent↗
PubMed1999

Gene-mutated HIV-1/SIV chimeric viruses as AIDS live attenuated vaccines for potential human use.

To develop an AIDS vaccine for human use as well as a suitable animal model for AIDS research, we constructed a series of HIV-1/SIVmac chimeric viruses (SHIVs). We successfully generated a SHIV (designated as NM-3rN) having the HIV-1 env gene, which enabled the evaluation of the efficacy of HIV-1 Env-targeted vaccines in macaque monkeys instead of chimpanzees. Two NM-3rN derivatives (NM-3 and NM-3n) induced long-term anti-virus immunities without manifesting the disease. The monkeys vaccinated with NM-3 or NM-3n became resistant to a challenge inoculation with NM-3rN. Serum from a monkey vaccinated with NM-3 neutralized not only the parental HIV-1 (NL432), but also an antigenically different HIV-1 (MN). In vivo experiments confirmed the heterologous protection against an SHIV having the HIV-1 (MN) env. In addition to specific immunity including neutralizing antibodies and cytotoxic T lymphocyte activity, nonspecific immunity such as natural killer activity is associated with this protection. These data suggest that the live vaccine has the ability to protect individuals against various types of HIVs. These SHIVs should contribute to the development of future anti-HIV-1 live vaccines in humans.

AIDS Vaccines↗
PubMed1999

Replication capacity of simian immunodeficiency virus in cultured macaque macrophages and dendritic cells is not prerequisite for intravaginal transmission of the virus in macaques.

In order to test the hypothesis that macrophages and dendritic cells (DCs) in mucosal tissue play an important role in heterosexual transmission of human immunodeficiency virus, the replication capacities of two simian immunodeficiency viruses (SIVs) were examined in cultured macrophages and DCs as well as in cultured PBMCs in vitro. The virus strains were a T cell-tropic SIV, SIVmac239, and a T cell- and macrophage-tropic (dual-tropic) SIV, SIVmac239/316E. The infectivities of these viruses to cynomolgus macaques by intravaginal inoculation were also compared. Although both virus strains replicated well in cultured PBMCs, SIVmac239 did not replicate in cultured macrophages, whereas SIVmac239/316E did. Both strains showed little replication in cultured DCs, but a high virus yield could be obtained when SIVmac239/316E-infected DCs were co-cultured with uninfected PBMCs. A mixture of these SIVs was inoculated intravaginally to three monkeys and the virus strain that first appeared through the vaginal mucosa was determined. The virus clones detected first in PBMCs, inguinal lymph nodes and vaginal wash cells (VWCs) after the virus inoculation were of SIVmac239 in all cases, except for one clone of SIVmac239/316E in VWCs of one monkey at one time-point. These results show that the infectivity of the virus in intravaginal transmission did not depend on the cell tropism in vitro of the virus.

Animals↗
PubMed1999

Human immunodeficiency virus type 1 intergroup (M/O) recombination in cameroon.

Here we describe, for the first time, recombinants between two highly divergent major groups of human immunodeficiency virus type 1 (HIV-1), M and O, within a Cameroonian woman infected with three different HIV-1 strains, a group O virus, a subtype D virus, and a recently reported IBNG (A/G)-like recombinant virus. Using nested extra-long PCR amplification, we sequenced from the pol region to the env region including accessory genes of the viral genome obtained from the patient's uncultured peripheral blood mononuclear cells and examined the phylogenetic position of each gene. Compared with sequential blood samples obtained in 1995 and 1996, there were multiple segmental exchanges between three HIV-1 strains (O, D, and IBNG) and all the recombinants appeared to be derived from a common M/O ancestor. Importantly, recombination between groups M and O occurred, even though the homology between these two groups is 69, 76, 68, and 55% in the gag, pol, vif-vpr, and env regions, respectively. Recombination between strains with such distant lineages may contribute substantially to generating new HIV-1 variants.

Adult↗
PubMed1999

[Intracerebral hemorrhage associated with long-lasting deficiency of factor XIII].

A 5-year-old boy had an intracerebral hematoma evacuated from the left parieto-occipital region at a local hospital. There was a difficulty in hemostasis during the operation. Postoperatively his neurological state gradually deteriorated. CT scans showed a gradual increase in intracerebral hemorrhage at the operated site. He was transferred to our clinic for further treatment. The preoperative blood coagulation profile showed that the activity of factor XIII was only 4%. The hematoma was removed without any trouble under administration of factor XIII. Postoperative course was also uneventful although the plasma level of factor XIII did not go up higher than 26% in spite of its daily administration. Although factor XIII administration was terminated one month after cranioplasty, the patient showed good recovery and the level of factor XIII spontaneously normalized in 6 months. The cause of the extremely low level of factor XIII in this case is not known, but it could be ascribed to massive hemorrhage.

Cerebral Hemorrhage↗
PubMed1998

Sero-epidemiologic and phylogenetic studies of HTLV-I infection in 2 countries of the Caspian Sea region.

Phylogenetic analysis of HTLV-I variants persisting among population of Turkmenistan and the Republic of Georgia (situated on both sides of the Caspian Sea, not far from a known HTLV-I cluster in Northern Iran) has been carried out. HTLV-I isolates from the above countries were obtained in the course of seroepidemiological investigations. In all, 1,510 blood-donor samples from Turkmenistan and 47 blood samples from hematological patients from Georgia, were tested with different screening and confirmatory assays, including commercial ones. As a result, 7 infected individuals (3 blood donors and 4 relatives of one blood donor) from Turkmenistan and 3 infected individuals (one ATL patient and 2 of his relatives) from Georgia were found. In addition, 4 HTLV-I isolates from Turkmenistan and one from Georgia were cloned and part of their LTR was sequenced. Phylogenetic analysis of sequenced isolates allowed us to conclude that these isolates belonged to sub-type A, one of 3 sub-types of the "Cosmopolitan" type. We found that most of the Turkmenian isolates formed a tight cluster and shared common nucleotide substitutions with isolates originating from Northern Iran (Mashhad). The data obtained suggest that there is a new endemic focus of HTLV-I infection in the Caspian Sea region. Further investigations are required to confirm this hypothesis.

Adolescent↗
PubMed1998

Various types of HIV mixed infections in Cameroon.

In order to assess the incidence of HIV mixed infection as well as to clarify the molecular epidemiology of HIV in central Africa, we investigated 43 HIVs obtained from 211 Cameroonian AC, ARC, and AIDS patients in 1994 and 1995. Part of the pol region and part of the env region were phylogenetically analyzed. The genotypes observed were varied: of 43 specimens, 28 (65%) were subtype A, 1 (2%) was subtype B, 2 (5%) were subtype D, 3 (7%) were subtype F, and 2 (5%) were group O. Of the remaining 7 specimens, 3 were mixed infections with HIV-1 subtypes A and C, HIV-1 subtypes C and F, and HIV-2 subtype A and HIV-1 subtype A; 1 was a mixed infection with HIV-1 subtypes A and D and the highly divergent group O (triple infection); another 3 appeared to consist of mosaic genomes (A/G, A/E, and B/A recombinant). These data show that various types of mixed infection, such as between different subtypes of HIV-1 group M, between HIV-1 and HIV-2, and even between HIV-1 groups O and M, were confirmed at a rather high frequency (approximately 10%). The mixed infection is particularly significant where there is a greater variety of HIV-1 subtypes circulating, since it results in new genetic diversity generated by intersubtype recombination.

Adolescent↗
PubMed1998

African origin of GB virus C/hepatitis G virus.

Ninety-four GB virus C/hepatitis G virus (GBV-C/ HGV) RNA-positive serum samples were obtained from all over the world. We found that all 15 GBV-C/HGV isolates from the Pygmies and the Bantu in the Central African region had a 12-amino acid indel (i.e. insertion or deletion) in the non-structural protein (NS) 5A region. Phylogenetic analyses of the NS5A region, using GBV-A as an outgroup, showed that these 15 isolates had diverged from the common ancestor much earlier than the remaining isolates, indicating an African origin of GBV-C/HGV.

Africa↗
PubMed1998

Lack of anti-GOR antibody among subjects with GB virus C/hepatitis G virus RNA.

Homologies were sought between the putative amino acid sequences of GB virus C/hepatitis G virus (GBV-C/HGV) and the GOR epitope or the liver/kidney microsome-1 (LKM-1) epitope, which share partial sequence identity with the hepatitis C virus (HCV) polyprotein. Anti-GOR antibody (anti-GOR) was assayed among 100 subjects with GBV-C/HGV RNA. Twenty-one and 25 subjects were coinfected with hepatitis B virus (HBV) or HCV, respectively. Homologies were found between the NS5 or E2 polyproteins of GBV-C/HGV and the GOR epitope or the LKM-1 epitope, respectively. These segments of GBV-C/HGV polyproteins sharing identity with the GOR or the LKM-1 epitope were well conserved among three genotypes of GBV-C/HGV. However, only 1 of 55 subjects (1.8%) with GBV-C/HGV RNA, but not with HBV or HCV, was positive for anti-GOR. The positivity for anti-GOR among the group with GBV-C/HGV RNA alone was significantly lower than that among the groups with HCV RNA (P < 0.01 and P < 0.05, respectively). Only 2 of 55 subjects (3.6%) with GBV-C/HGV RNA alone exhibited elevation of alanine aminotransferase. The incidence of liver dysfunction among the group with GBV-C/HGV RNA alone was significantly lower than the incidence among the groups with GBV-C/HGV RNA and hepatitis B surface antigen (HBsAg) or HCV RNA (P< 0.01 and P< 0.01, respectively). These data indicate that 1) there is no association between GBV-C/HGV infection and the presence of anti-GOR, and 2) GBV-C/HGV infection is not related to chronic liver dysfunction.

Adult↗
PubMed1998

HTLV-Is in Argentina are phylogenetically similar to those of other South American countries, but different from HTLV-Is in Africa.

To understand the origin and past dissemination of human T-cell leukemia/lymphotropic virus type I (HTLV-I) in Latin America, we conducted a phylogenetic study of five new HTLV-I isolates from Argentina. We sequenced partial fragments of long terminal repeats (LTR) of the new HTLV-Is, and then the sequences were subjected to a phylogenetic analysis for comparison with other HTLV-Is of various geographical origins. Our results indicated that all the isolates were members of the Cosmopolitan group. Furthermore, most (four out of five isolates) of the new HTLV-Is belonged to the Transcontinental (A) subgroup, the most widespread subgroup of the four subgroups in the Cosmopolitan group. In this subgroup, they were closely related to HTLV-Is found in other South American countries including those of Amerindians, and were different from those found in Africa. In contrast, the remaining one HTLV-I (ARGMF) did not show any clear similarity to known HTLV-I isolates belonging to the Cosmopolitan group. The close similarity of South American HTLV-Is strongly suggests a common origin of the virus in this continent. Our results do not support the proposed idea of recent introduction of HTLV-I into South America as a consequence of the slave trade from Africa, where phylogenetically different HTLV-Is predominate.

Africa↗
PubMed1998

Fas antigen expression and apoptosis of lymphocytes in macaques infected with simian immunodeficiency virus strain mac.

To investigate the role of apoptosis in the pathogenesis of HIV infection we used macaques infected with simian immunodeficiency virus (SIV) as a primate model and examined the characteristics of the apoptosis of lymphocytes in SIV mac-infected macaques. In vitro apoptosis was more strongly induced in peripheral blood mononuclear cells (PBMC) from SIV mac239-infected macaques than those from uninfected controls. We found that the frequency of Fas antigen-positive cells was higher in PBMC from SIV mac-infected macaques than from uninfected controls, and in vitro apoptosis of PBMC was suppressed by an inhibitor of the interleukin-1 beta converting enzyme (ICE) family proteases. In biopsied lymph nodes, the number of apoptotic nuclei in T cell-dependent areas was higher in SIV mac-infected macaques than in uninfected controls. A higher number of apoptotic nuclei in lymph nodes of SIV mac-infected macaques was observed in the stage of persistent general lymphadenopathy than in those with AIDS-related complex, while there was no significant difference in the extent of apoptosis of cultured PBMC among the SIV mac-infected macaques. These results suggest that in vitro apoptosis is mediated by the Fas/Fas ligand and ICE system and that apoptosis in lymph nodes may be more closely related to the stage of SIV mac infection than is that of cultured PBMC.

Animals↗
PubMed1998

Replication of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus strain mac (SIVmac) and chimeric HIV-1/SIVmac viruses having env genes derived from macrophage-tropic viruses: an indication of different mechanisms of macrophage-tropism in human and monkey cells.

To investigate the transferability of macrophage (Mphi)-tropism among primate lentiviruses, we constructed recombinants of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus strain mac (SIVmac) and chimeric HIV-1/SIVmac (SHIV) having env region Mphi-tropic determinants. A recombinant HIV-1 having env partially derived from a Mphi-tropic HIV-1 strain (JR-FL) replicated in human macrophages but not in monkey macrophages. Conversely, a recombinant SIVmac having env from a Mphi-tropic strain (SIVmac316) replicated in monkey macrophages but not in human macrophages. A new SHIV (designated NM-3rN/JRFL) carrying the LTR and gag, pol, vif, vpx and nef of SIVmac and vpr, tat, rev, vpu and env of HIV-1 with env partially replaced by that of JR-FL was replication-competent in human macrophages but not in monkey macrophages. These results suggest that the Mphi-tropic determinant is specific to each host species and that the mechanism of Mphi-tropism is different between HIV and SIV.

Animals↗
PubMed1998

Infectivity and immunogenicity of SIVmac/HIV-1 chimeric viruses (SHIVs) with deletions in two or three genes (vpr, nef and vpx).

Two SHIVs with two or three genes deleted (SHIV-drn and SHIV-dxrn) were constructed. The inoculation of monkeys with SHIV-drn resulted in short-term viremia, but inoculation with SHIV-dxrn did not. At 68 weeks post-inoculation, the monkeys were reinoculated with a 100-fold higher dose of each SHIV, but none showed viremia. Killer cell activities against HIV-1 Env were detected in the SHIV-drn- and SHIV-dxrn-inoculated monkeys. Cross-reactive killer activity against HIV-1 Gag and SIVmac Gag was observed in one monkey. Antibodies were not detected in the SHIV-dxrn-inoculated monkeys, but the SHIV-drn-inoculated monkeys showed an anamnestic antibody reaction. These data indicate that SHIV-drn is infectious to and immuno-inducible in macaques but SHIV-dxrn is not.

AIDS Vaccines↗
PubMed1998

Construction of the chimeric reverse transcriptase of simian immunodeficiency virus sensitive to nonnucleoside reverse transcriptase inhibitor.

A number of structurally diverse compounds have been shown to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The compounds can be grouped into two broad classes; nucleoside analogs and nonnucleoside RT inhibitors. The nonnucleoside RT inhibitors are quite specific for HIV-1 RT but not human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) RT. We have investigated the property of SIV/HIV-1 chimeric viruses in which portions of SIV(MAC) RT were exchanged with the corresponding domain of HIV-1 RT; amino acids 176-190, 176-383 and 176-495 of HIV-1 RT. The chimeric virus, which was substituted amino acids 176-190 of RT, had detectable RT activity, and this chimeric RT was sensitive to three nonnucleoside RT inhibitors [nevirapine, HEPT derivative (E-EBU-dM) and TIBO derivative (R82913)]. To further study this chimeric virus, we purified the chimeric RT enzyme expressed in Escherichia coli and determined its kinetic properties; the Km, and Vmax values, and the Ki value of HEPT derivative calculated for the DNA polymerase activity. This study reveals that amino acids 176-190 of SIV(MAC) RT were important for the enzymatic activity and the SIV/HIV-1 chimeric RT, which had amino acids 176-190 of HIV-1, was sensitive to the nonnucleoside RT inhibitor.

Amino Acid Sequence↗
PubMed1998

A new approach to AIDS research and prevention: the use of gene-mutated HIV-1/SIV chimeric viruses for anti-HIV-1 live-attenuated vaccines.

The lack of a suitable animal model is a major obstacle to developing anti-HIV-1 vaccines. We successfully generated an SIVmac/HIV-1 chimeric virus (SHIV) (designated as NM-3rN) that contains the HIV-1 env gene and is infectious to macaque monkeys. Challenging the vaccinated macaque monkeys with NM-3rN, we developed an evaluation system for anti-HIV-1 Env-targeted vaccines. For the purpose of making the vaccine, a series of gene-mutated SHIVs were constructed. The monkeys vaccinated with these SHIVs had long-term anti-virus immunities without manifesting the disease, and became resistant to a challenge inoculation with NM-3rN. The sera from a monkey showed that, after the vaccination, the neutralizing antibodies not only against the parental HIV-1 but also against an antigenically different HIV-1 were raised. In vivo experiments confirmed that the vaccinated monkeys were protected from the challenge inoculum of an antigenically different SHIV-MN. Vaccination of monkeys with the attenuated SHIVs showed that further gene-deletion of the SHIV resulted in less immunogenicity. Nevertheless, the attenuated SHIVs had a vaccine effect against the challenge inoculation. In addition to specific immunities including neutralizing antibodies and cytotoxic T cells, a more complicated immune mechanism induced by live vaccine appears to play a role in this protection. Our data suggest that the live vaccine can induce strong and wide-range immunity against HIV-1. These SHIVs should contribute to understanding the pathogenicity of AIDS and to the development of future anti-HIV-1 live vaccines for humans.

AIDS Vaccines↗