Hematopoietic viral infections

Chemokines are a superfamily of small proteins which play a crucial role in immune and inflammatory reactions and in viral infection (Hedrick and Zlotnik, 1996 Baggi-olini et al, 1997 Rollins, 1997). Most chemokines cause migration of leukocytes, but these molecules also affect angiogenesis, proliferation of hematopoietic precursors, and viral responses. Based on a cysteine motif, a CXC, CC, C and CX3C family have been identified (Fig. 1). CXC (or a) chemokines are active on neutrophils and lymphocytes while CC (or (3) chemokines exert their action on multiple leukocyte subtypes, including monocytes, basophils, eosinophils, T-lymphocytes, dendritic cells (DC) and NK cells, but they are generally inactive on PMN. Eotaxins... 

Hematopoietic progenitor cells Bailey et al. (2006) Reseeding of a viral variant from a rare infection event of a few progenitor cells raises the possibility that the bone marrow compartment may be a source of latent provirus... 

The overall effect of Li+ on the hematopoietic system is of stimulation of the immune system. Not surprisingly then, Li+ is reported to exacerbate the activity of a number of autoimmune diseases, such as psoriasis [212] and rheumatoid arthritis [213], and to result in the production of autoantibodies in some patients [214]. However, there is no evidence that Li+ s stimulation of the immune system leads to any reduction in the occurrence of viral or bacterial infections in patients on Li+ therapy. 

AIDS is associated with aberrant lymphocyte production and it has been proposed that Li+ may have a potential role in reversing this. Additionally, 3 -azido-3"deoxythymidine (AZT, zidovudine), an effective inhibitor of viral reverse transcriptase that reduces mortality in AIDS patients, induces hematopoietic suppression in patients resulting in anemia, neutropenia, and overall bone-marrow failure [220]. In murine AIDS, the coadministration of Li+ effectively moderates this toxicity of AZT in vivo [221,222]. There are several case reports where Li+ has been administered to help reduce the hematopoietic suppression in HIV-infected patients taking AZT (for example, see ref. 223). To date, the use of Li+ has been limited to a few weeks of treatment, and varying degrees of success have been achieved nevertheless the outlook in this field is quite hopeful. 

Whole oiganisms and glycoprotein-rich hot-water extracts of C. vulgaris strain CK show not only an antitumor immuno-potentiation [9,10,44] but also a protective effect on bacterial [12,13,15,24,25] and viral [14] infections in murine systems. Hot-water extracts accelerate the recovery of neutrophils and restore protection against infection with K coli in neutropenic states by a cyclophosphamide treatment [13,15], Thus, glycoprotein-rich extracts may not only activate mature leukocytes but also stimulate hematopoietic stem cells in the bone marrow. 

Fluman CMV replication in the natural host is not well understood. Viral pathogenesis, tropism for epithelial and endothelial cells, and immune clearance mechanisms are generally believed to be similar to murine CMV, but there are important distinctions as well (Koszinowski et al. 1990 Pass 2001). In natural infections with human CMV, viremia persists for months to years after initial infection, accompanied by persistent replication and asymptomatic shedding of virus in both saliva and urine (Revello et al. 1998). Eventually, viral replication is believed to be brought under control by the development of an adaptive immune response where the contribution of a virus-specific CTL response to clearance is well documented in patient populations (Riddell and Greenberg 1997). Virus remains latent in hematopoietic progenitors, sporadically reactivates, and is shed in saliva. 

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