No abstract

Plasmodium falciparum-infected human erythrocytes evade host immunity by expression of a cell-surface variant antigen and receptors for adherence to endothelial cells. These properties have been ascribed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), an antigenically diverse malarial protein of 200-350 kDa on the surface of parasitized erythrocytes (PEs). We describe the cloning of two related PfEMP1 genes from the Malayan Camp (MC) parasite strain. Antibodies generated against recombinant protein fragments of the genes were specific for MC strain PfEMP1 protein. These antibodies reacted only with the surface of MC strain PEs and blocked adherence of these cells to CD36 but without effect on adherence to thrombospondin. Multiple forms of the PfEMP1 gene are apparent in MC parasites. The molecular basis for antigenic variation in malaria and adherence of infected erythrocytes to host cells can now be pursued.

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN.

Long-term cultures were established of HTLV-III-infected T4 cells from patients with the acquired immune deficiency syndrome (AIDS) and of T4 cells from normal donors after infection of the cells in vitro. By initially reducing the number of cells per milliliter of culture medium it was possible to grow the infected cells for 50 to 60 days. As with uninfected T cells, immunologic activation of the HTLV-III-infected cells with phytohemagglutinin led to patterns of gene expression typical of T-cell differentiation, such as production of interleukin-2 and expression of interleukin-2 receptors, but in the infected cells immunologic activation also led to expression of HTLV-III, which was followed by cell death. The results revealed a cytopathogenic mechanism that may account for T4 cell depletion in AIDS patients and suggest how repeated antigenic stimulation by infectious agents, such as malaria in Africa, or by allogeneic blood or semen, may be important determinants of the latency period in AIDS.

H-2 gene transfection was used to restore expression of H-2K antigens in metastatic and non-metastatic subclones of a murine fibrosarcoma that lack their major histocompatibility complex-encoded H-2K antigens. De novo expression of H-2K reduced tumorigenicity and abolished the formation of metastasis in syngeneic mice. Expression of H-2K may lead to effective recognition of the disseminating tumour cells by the host immune system.