An increasing number of viruses are known to infect lymphocytes, and directly or indirectly induce lymphocyte proliferation. Both retroviruses and DNA viruses infect lymphocytes. Human GD4 ' T cells are infected by the nontransforming retroviruses human immunodeficiency virus type 1 (HIV-1) and HIV-2 and by the transforming retrovirus human T lympho-tropic virus type I (HTLV-I) while CDS cells are transformed by HTLV-I. Human B cells are infected with two herpesviruses: Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV8). Likewise, human T cells are infected with at least three herpesviruses: HHV6 and HHV7 and herpesvirus saimiri. Mouse B cells are infected with murine mammary tumor virus (MMTV), resulting in augmented T and B cell proliferation. Other organisms have subverted lymphocyte signal transduction pathways for enhanced rep-licative fitness, to impair the host immune response or both. A list of some of these agents and their targets are found in Table 4.
Table 4 Examples of pathogens that can alter lymphocyte prolieration
Feline leukemia virus (FeLV) Bovine leukemia virus (BLV)
Infects CD4 cells via CD4 and chemokine coreceptors env gp120 primes uninfected CD4 T cells for antigen-induced apoptosis net p27 perturbs TCR signal transduction, and may predispose thymocytes to negative selection
HIV gag proteins bind to cyclophilins A and B via a cyclosporine-inhibitable interaction, and gag:CyP binding may inhibit T cell activation Vpr gene product arrests infected T cells in the G2+M phase of the cell cycle Transforms T cells. An immunosuppressive peptide homologous to the p15E product of FeLV,
MuLV, and HTLV-I inhibits protein kinase C-dependent responses FeLV-infected lymphocytes have impaired calcium mobilization to a variety of stimuli BLV can transform bovine lymphocytes. The env gene for BLV encodes a TAM motif, and this may induce aberrant or constitutive signal transduction through the Src family of protein tyrosine kinases
Poxviruses produce soluble IL-1 and tumor necrosis factor a (TNFa) binding proteins that inhibit cytokine signals by ligand:receptor competition LMP2A, a transmembrane protein of Epstein-Barr virus, encodes a TAM motif, and signal transduction via the motif may contribute to immortalization of B cells The binding of EBV to the B cell receptor CR2 elevates calcium, and may be involved in the initial infection of B cells. EBV-transformed B cells have impaired antigen receptor-induced calcium mobilization Infects T cells and increases CD4 expression. Transactivates HIV expression. Infects human CD4 cells. Uses CD4 as a receptor Some strains transform human T cells
Infects mouse B cells, and causes superantigen specific T cell proliferation
T cell activation induced by microbial superantigens, and this may induce proliferation or apoptosis of T cells
T. parvum is an intracellular parasite that can transform bovine lymphocytes and causes constitutive IL-2 mRNA expression
From Siegel JN and June CH (1995) Signal transduction and T lymphocyte activation. In: Rich RR (ed) Principles of Clinical Immunology. St Louis, MO: Mosby Year Book.
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