Donna R. Sasso

Involvement of Matrix Metalloproteinases in Human Immunodeficiency Virus Type 1-Induced Replication by Clinical Mycobacterium avium Isolates

The role of Mycobacterium avium isolates in modulating human immunodeficiency virus type 1 (HIV-1) replication was examined by use of an in vitro, resting T cell system. Two human clinical isolates (serotypes 1 and 4) but not an environmental M. avium isolate (serotype 2) enhanced HIV-1 replication. The M. avium-induced HIV-1 replication was not associated with cell activation or differential cytokine production or utilization. Addition of matrix metalloproteinase (MMP) inhibitors and their in vivo regulators, tissue inhibitors of metalloproteinases-1 and -2, abrogated M. avium-induced HIV-1 replication 80%-95%. The MMP inhibitors did not have any effect on the HIV-1 protease activity, suggesting that they may affect cellular processes. Furthermore, MMP-9 protein was differentially expressed after infection with clinical M. avium isolates and paralleled HIV-1 p24 production. Collectively, these data suggest that M. avium-induced HIV-1 replication is mediated, in part, through the induction of MMP-9.

Humans with OKT4-epitope deficiency have a single nucleotide base change in the CD4 gene, resulting in substitution of TRP240 for ARG240☆

The OKT4 epitope of the CD4 cell-surface protein has been shown to be polymorphic in white, black, and Japanese populations. The variable phenotypic expression is due to an alteration of the OKT4 epitope, since those persons lacking reactivity with OKT4 monoclonal antibody (mAb) are reactive with OKT4A-F mAb as well as other mAb specific for CD4. To determine the nature of this polymorphism at the gene level, we sequenced polymerase chain reaction-amplified genomic DNA containing the CD4-V3 and -V4 exons from American black subjects who are OKT4-normal, OKT4-negative heterozygous, or OKT4-negative homozygous. Comparison of the sequences revealed that the two CD4 exons are identical except for a cytosine-to-thymidine transition occurring at nucleotide position 868. This alters the first codon position of mino acid 240 and results in a tryptophan residue replacing an arginine residue. The change was also found in white and Japanese persons who are OKT4-negative.

Down-Regulation of Interleukin-10 Expression and Production Is Associated with Spontaneous Proliferation by Lymphocytes from Human T Lymphotropic Virus Type II-Infected Persons

Cytokines from peripheral blood mononuclear cells (PBMC) from human T lymphotropic virus (HTLV)-II-infected persons were studied to delineate the mechanism(s) of spontaneous lymphocyte proliferation (SLP). Culturing HTLV-II-infected PBMC that spontaneously proliferate (SLP+) resulted in greater mRNA expression and production of interferon-gamma, interleukin (IL)-4, and IL-5, with a concomitant decrease in IL-10, than was seen with nonproliferating (SLP ) and normal PBMC. While IL-2 mRNA expression was higher, production was lower in SLP+ PBMC than in SLP and normal PBMC, implying that the proliferating cells are utilizing IL-2. Neutralization of IL-2 resulted in partial inhibition, suggesting that other cytokines also affect SLP. Addition of recombinant IL-10 inhibited the proliferation of SLP+ PBMC. Further, blocking costimulatory signals with monoclonal antibodies against CD80/CD86 resulted in increased IL-10 production with concomitant inhibition of SLP. The mechanism(s) underlying HTLV-II-associated SLP in vitro involve increased utilization of IL-2 and down-regulation of IL-10.

Relationships of anopheles A group arboviruses.

Summary Anopheles A, Lukuni, and six serologically related viruses were partially characterized in mice and cell cultures and were cross-tested by a variety of serologic methods. Hemagglutinins were not successfully produced; complement-fixation (CF) demonstrated extensive cross reactivity and was, therefore, of little value in distinguishing between strains; precipitin testing by double diffusion in agar supported the CF test results but these tests were too specific to be useful in showing relationships. When neutralization tests were performed, the relationship between the eight strains became apparent. Based on the latter test, a provisional classification of the Anopheles A group was proposed.