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porcine organ, with months to years of viral exposure, has not yet been addressed. Retroviral transmission from swine to human is likely to be dependent upon several factors, including degree of retroviral activation (i.e., viral load), as well as recipient immune responses. Unfortunately, many conditions associated with retroviral activation are present in the transplant recipient; these include exogenous immunosuppression, graft rejection, and viral confection. It remains to be determined to what extent PERV viral load is effected by any of these variables.

The sensitivity of mammalian C-type retroviruses such as PERV to inactivation by human serum has recently been shown to depend upon the expression of alpha gal antigen. In so far as dismantling of the host aGal response has been critical to overcoming hyperacute xenograft rejection, it stands to reason that successful xenotransplantation will depend upon deliberate creation of a milieu most favorable to PERV transmission. The exact contribution of anti aGal antibody and complement to neutralization of PERV has not been completely explored.

Retroviral infections often cause severe immunosuppression in many species, opening the door to opportunistic infections leading to fatal disorders). Severity of retrovirus induced immunosuppression has been shown to depend upon viral load, an association clearly observed with HIV and AIDS. The effect of PERV infection upon human immune responses has not been investigated, nor has the immunomodulatory effect(s) of PERV infection been correlated with viral load. Clearly, the issue of PERV will need to be addressed, along with other potential zoonotic agents, as we move toward clinical pig-to-human transplantation.

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