ENDOGENOUS RETROVIRUSES AND RESISTANCE TO EXOGENOUS RETROVIRUS INFECTION

Endogenous proviruses have

been accumulating in the human genome over a period of tens of millions of years

and currently comprise around 8% of human DNA.  It seems reasonable to suppose

that during this time a process of co-evolution has occurred, with the

development of host mechanisms to control virus expression and a series of virus

counter-measures.  In addition, it would not be surprising if specific proviral

products might take on niche functions benefiting the host, perhaps in providing

In the mouse, a number of

genes for resistance to retroviral infection have been described. One of these,

Fv1, acts in a cell autonomous manner to block infection at a post-penetration,

pre-integration stage in the viral life cycle.  We have cloned Fv1 by positional

means.  It is related to sequences encoding part of the gag gene of the

MuERV-L/HERV-L family of endogenous proviruses.  More recently, phenotypically

similar activities have been detected in cells from a variety of primates,

In light of the apparent

similarities between Fv1 and Ref1/Lv1, it is tempting to speculate that the

latter genes are also of endogenous proviral origin.  In collaboration with Drs.

Jonas Blomberg and Michael Tristram we are developing a candidate gene strategy

for attempting the cloning of Ref1/Lv1.  A large collection of ERVs with open

reading frames in gag has been identified by bioinformatics means. They are

currently being cloned into an expression vector for functional testing of

antiretroviral activity.  Progress and programs with associating specific