Anti-viral immunity

The activation of DRF-3 through the TREF dependent pathway allows for chemokines such as RANTES to be produced. It also leads to the production of DFN-a and EFN-(3, which are involved in anti-viral immunity. The TREF pathway, activated by either TLR-3 or TLR-4, can also induce MHC class-II expression and costimulatory molecules, thus leading to T-cell activation. This provides an important link between innate and adaptive immunity. 

Peiipheral anti-viral immune responses control in measure HIV-1 CNS infection... 

Besides the role of retinoids in host immune defenses to viral infections (see [6] for review), retinoids may also affect virus replication. Angulo et al. [44] characterized three RA response elements in the promoter region of human cytomegalovirus (hCMV) and demonstrated the necessity for RAR and RXR in the viral promoter s positive response to RA. In contrast, the replication of herpes simplex virus-1 (HSV-1) in cultured Vero cells was inhibited by isomers of RA, but not retinol inhibition occurred without evident induction of IFN-a or IFN-p gene expression [45]. RA also protected HL-60 and WISH cells from infection with vesicular stomatitis virus (VSV) [46] however, in this case RA significantly increased the ability of IFN-a to decrease virus replication. These apparently contrasting effects of RA on hCMV as compared to HSV-1 or VSV replication further illustrate the potential for retinoids to act either positively or negatively in host resistance to viral infection and anti-viral immunity. Retinoid-IFN interactions are further discussed later in this chapter. 

Concurrent injection of a rhabdovirus-specific DNA vaccine with a polyvalent, oil-adjuvanted vaccine delays the specific anti-viral immune response in Atlantic Salmon, Salmo solar L. Fish Shellfish Immunol 2010a, 28,579-586. 

Ahmed RK, Nilsson C, Biberfeld G, Thorstensson R. Role of CD8+ cell-produced anti-viral factors in protective immunity in HIV-2-exposed but seronegative macaques resistant to intrarectal SIVsm challenge. Scand J Immunol 2001 53 245-253. 

Sheridan, I.F. et al.., Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice, J. Neuroimmunol., 31, 245, 1991. 

IFN-y exhibits at best weak anti-viral and anti-proliferative activity. When co-administered with type I IFNs, however, it potentates these IFN-a/jS activities. IFN-y is directly involved in regulating most aspects of the immune and inflammatory responses. It promotes activation, growth and differentiation of a wide variety of cell types involved in these physiological processes (Table 4.7). 

The anti-viral and anti-proliferative activity of IFNs, as well as their ability to modulate the immune and inflammatory response, renders obvious their potential medical application. This has culminated in the approval for clinical use of several interferon preparations (Table 4.8). 

Although infected individuals display a wide range of anti-viral immunological responses, these ultimately fail to destroy the virus. A greater understanding of what elements of immunity are most effective in combating HIV infection is required. 

Although the primary objective of any vaccine is its prophylactic use (i.e. prevention of future occurrence of a disease), AIDS vaccines may also be of therapeutic value. This supposition is based upon the fact that the immune system controls the viral infection for a time period. Hence, any agent capable of enhancing the anti-HIV immune response may prolong this elfect. 

Mother s milk is an often coined term for products that mimic the natural mother s milk contents. Actual human mother s milk contains about 40-50% casein and 50-60% whey, and about 17% lactoferrin with no beta-lactoglobulin. As I said earlier, mother s milk contains alfa lactoglobulin. This is very different from cow s milk which contains about 80% casein and 20% whey with 1% lactoferrin being average. Lactoferrin has anti-viral activity, and is a potent immune system booster. Obviously this is an advantage for new born human (rug rats) since they lack complete immune system functions. Remember the fact that human mother s milk dominant protein fraction is alfa-lactalbumin Well, there is a research project on going which claims acid folded alfa-... 

Proteins are also used clinically to treat a variety of diseases. Erythropoietin stimulates erythrocyte production in kidney dialysis and chemotherapy patients. Granulocyte stimulating factor enhances immune systems compromised by cancer treatments. Cytokines such as interferons and interleukins are used for their anti-viral and anti-tumor activities. Other proteins are used to inhibit or stimulate blood clotting. For the most part, the pharmaceutical protein industry relies on cloning native human genes and expressing and purifying their products in recombinant form. 

IFN-y is a potent immunostimulatory and anti-viral cytokine. The frequency of specific IFN-y-secreting cells stimulated by liposomal formulations exclusively containing the CTL epitope NS 18 51 or combinations with CpG, respectively, was evaluated by ELISPOT assay. Two weeks after three immunizations, high numbers of specific IFN-y-secreting cells in mice immunized with liposomes containing NS1851 (-0.2% of total spleen cells) were detected which further increased in mice immunized with liposomal formulations containing CpG (-0.7% of total spleen cells) (Fig. lb). 

Hemmi, H., Kaisho, T., Takeuchi, O., Sato, S., Sanjo, H., Hoshino, K., Horshino, T., Tomizawa, H., Takeda, K. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signalling pathway. Nat. Immunol. 2002, 5(2), 196-200. 

A variety of mammalian cellular systems have been used as experimental models for documenting the in vitro effects of cannabinoids on immune responsiveness to viruses, bacteria, and amoebae. Blevins and Dumic (1980) indicated that THC had a protective effect against HSV infection in vitro. It was found that both HSV-1 and HSV-2 failed to replicate and produce extensive cytopathic effect (c.p.e.) in human cell monolayer cultures exposed before infection, at infection, or post infection to various concentrations of THC. In contrast, other studies indicate that THC compromises resistance to virus infection. It has been reported that THC inhibits macrophage extrinsic anti-viral activity (Cabral and Vasquez 1991 Cabral and Vdsquez 1992) whereby macrophages normally suppress virus replication in cells to which they attach (Morahan et al. 1980 Stohlman et al. 1982). Noe et al. (1998) reported that a variety of cannabinoid receptor agonists enhanced syncytia formation in human T cell leukemia virus-I (HTLV-I)-transformed human T (MT-2) cells infected with cell free human immunodeficiency virus (HIV-IMN). It was found that CP 55,940, THC, WIN 55,212-2, and WIN 55,212-3 significantly increased syncytia formation, a phenomenon that has been reported to serve as an indicator of HIV infection and cytopathicity. 

In contrast to zanamivir (8), oseltamivir (9) is an oral anti-viral drug for the treatment cf uncomplicated influenza in patients whose flu symptoms have not lasted more than 2 days (15, 16). This product treats types A and B influenza however, the majority of patients in the United States are infected with type A. FTTit ay of oseltamivir (9) in the treatment of influenza in subjects with chronic cardiac disease and/or respiratory disease has not been established. Oseltamivir (9) is also approved for the prevention of influenza in adults and adolescents older than 13 years. Efficacy of oseltamivir (9) for the prevention of influenza has not been established in immune-compromisedpatients. 

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