Helicobacter pylori infection in peptic ulcer disease and gastric malignancy.

Helicobacter pylori infection is the world's most common chronic infection in humans and is the cause of most gastritis cases. This infection is accepted as the etiology of the majority of peptic ulcers. It has been implicated as a significant contributing factor in the development of gastric malignancy--both gastric MALT lymphoma and gastric adenocarcinoma. Both endoscopic and non-endoscopic tests are available for accurate diagnosis of the infection. Several multi-drug regimens are useful for effective eradication of the infection. Strategies have been developed for managing patients with gastric MALT lymphoma. Criteria to identify populations with increased risk for gastric malignancy are being developed. H. pylori induces gastritis; it is also involved in both apoptosis and cellular proliferation. The role of H. pylori infection in the pathogenesis of premalignant lesions, altered gastric acid secretion, and significant clinical presentations is the subject of numerous studies worldwide.

Identification of HIV1 determinants for T lymphoid cell line infection.

Determinants responsible for HIV-1 infection of T lymphoid cell lines were identified by functional analysis of chimeric proviral clones derived from T-cell line tropic-(HXB2) and non-T-cell line-tropic isolates (YU2, ADA). Replacement of the HXB2 V3 envelope loop sequence with that derived from YU2 resulted in a virus that is no longer T cell line-tropic. However, the reciprocal replacement using HXB2 V3 loop sequences did not confer upon either ADA or YU2 envelope proteins the ability to infect T cell lines. Furthermore, the resultant viruses were incapable of infection of primary lymphocytes. Single, double, and multiple point mutations made within the V3 loop sequence did not result in change in tropism, although mutations involving residue 275 resulted in a virus that was incapable of infecting primary lymphocytes but retained the ability to infect Jurkat T lymphoid cells. These results suggest that the V3 envelope determinant is necessary for T cell line infection, but other determinant(s) in envelope are also necessary to obtain infectious virus expression.

Dual regulation of silent and productive infection in monocytes by distinct human immunodeficiency virus type 1 determinants.

The regulation of human immunodeficiency virus type 1 infection and replication in primary monocytes was investigated by mutagenesis of recombinant proviral clones containing an env determinant required for the infectivity of monocytes. Virus replication was assayed by determination of reverse transcriptase activity in culture fluids and by recovery of virus from monocytes following cocultivation with uninfected peripheral blood mononuclear cells. Three virus replication phenotypes were observed in monocytes: productive infection, silent infection, and no infection. Incorporation of the monocytetropic env determinant in a full-length clone incapable of infection or replication in primary monocytes (no infection) conferred the capacity for highly efficient virus replication in monocytes (productive infection). Clones with the env determinant but lacking either functional vpr or vpu genes generated lower replication levels in monocytes. Mutation of both vpr and vpu, however, resulted in nearly complete attenuation of virus replication in monocytes, despite subsequent virus recovery from infected monocytes by cocultivation with uninfected peripheral blood mononuclear cells (silent infection). These findings indicate a central role for the "accessory" genes vpu and vpr in productive human immunodeficiency virus type 1 replication in monocytes and indicate that vpu and vpr may be capable of functional complementation.

Macrophage tropism determinants of human immunodeficiency virus type 1 in vivo.

Strains of human immunodeficiency virus type 1 differ in their abilities to infect and replicate in primary human macrophages. Chimeric clones were constructed from a provirus unable to infect macrophages (NLHX) and envelope sequences (V3 loop) of viruses derived without cultivation from brain (YU2 and w1-1c1) or spleen (w2-1b4) tissues. The substituted V3 loop sequences in each case were sufficient to confer upon NLHX the ability to infect macrophages. Furthermore, an envelope domain immediately N terminal to the V3 loop also was found to modulate the level of replication in macrophages. These results demonstrate that an envelope determinant derived directly from patients with AIDS confers HIV-1 tropism for macrophages.

Nucleotide sequence analysis of isolates of human T-lymphotropic virus type 1 of diverse geographical origins.

Nucleotide sequences for long terminal repeat (LTR), gag, the protease gene, and pol of a human T-lymphotropic virus type 1 (HTLV-1) isolate of probable Caribbean origin (HTLV-1CH) and a Zairian isolate (HTLV-1EL) were determined providing complete proviral sequences for these isolates. These sequences were compared with those available from previously analyzed isolates. Nucleotide sequence differences of 1.2-3.3% were identified among isolates for which complete genetic information was available. Nucleotide sequence diversity was distributed relatively evenly over the genome with 1.3-5.2% differences in the LTR, 1.1-2.9% differences in gag, 0.7-2.1% differences in the protease gene, 0.9-2.5% differences in pol, 0.9-2.4% differences in env, 0.0-1.4% differences in rex, and 0.1-2.6% differences in tax. There were 1.2-2.3% amino acid differences overall, with 0.8-1.6% nonconservative amino acid alterations. Nucleotide differences were not found in regions of the LTR which are important for transcriptional activity or Tax response. Within the Rex-response element, nucleotide differences were found predominantly in loop rather than stem structures, thus, maintaining the overall secondary structure necessary for Rex activity. Evolutionary tree analysis of the sequence differences suggests a predominant clustering of different HTLV1 strains according to geographical origin. An open reading frame was also identified on the minus DNA strand situated between the env and rex/tax genes which exhibits 0.1-6.9% nucleotide sequence variation among HTLV1 strains. The limited sequence variation among HTLV-1 strains is in striking contrast to the extensive heterogeneity seen among human immunodeficiency virus (HIV) strains.

Limited sequence heterogeneity among biologically distinct human immunodeficiency virus type 1 isolates from individuals involved in a clustered infectious outbreak.

Human immunodeficiency virus type 1 isolates were obtained over a 3-year period from blood, brain, and lung of three patients in a clustered infectious outbreak. This included a blood donor who was initially asymptomatic but subsequently developed AIDS-related complex and two neonatal transfusion recipients who developed AIDS. Isolates from brain and lung replicated to greater than 30-fold higher levels in primary monocyte cultures than did those from blood; no growth differences on primary lymphocytes were observed. Thirteen clones were obtained from seven isolates, and env sequences were determined. The predicted amino acid sequences among these clones differed by only 0.01% but differed by 15-27% when compared to previously sequenced isolates from other patients. The level of envelope amino acid sequence divergence noted among these isolates is considerably lower than that previously reported for other human immunodeficiency virus isolates. No differences in the envelope unique to lung or brain isolates compared to blood isolates were noted. This study provides evidence that mutations in the envelope may not be necessary for disease progression and that other portions of the viral genome may contribute to cell-specific tropism.