Christopher Tipper and John Coffin, Tufts University



In the history of their

co-existence, mice of the genus Mus and the gammaretrovirus MLV have

undergone several periods of expansion and diversification, making them ideal

subjects for studying the evolution of the host-retrovirus relationship.  An

endogenous MLV provirus identified in our lab, HEMV, represents a distinct step

in this co-evolution.  The provirus, to date identified only in the genome of

Mus spicilegus, is a member of a novel MLV group.  Species tropism and

interference studies have demonstrated that the HEMV env gene product

confers a unique infection pattern, limited to cells of Mus origin, and

utilizes a receptor distinct from other MLV’s.  Blotting experiments have

demonstrated that HEMV belongs to a group of viruses broadly distributed

throughout murine species and subspecies.  In addition, phylogenetic analysis

based upon both LTR and env sequences places this provirus in a central

position relative not only to the MLV’s but also to other MLV-like

gammaretroviruses.  Finally, the HEMV LTR and env sequences display a

much simpler structure than other MLV’s.  These data have led us to the

hypothesis that, despite the functionality of Env, the HEMV provirus represents

an ancient insertion of a virus closely related to the common progenitor of

MLVs, FeLV, GaLV and related viruses.


However, recent results

have challenged this hypothesis.  The HEMV gag, pro and part of the

pol genes, along with the previously cloned env gene, appear to be

intact.  The LTR’s are identical, consistent with a relatively recent

integration.  Most essential catalytic sites and domains of all sequenced

proteins appear to be present.  Nevertheless, the HEMV proteins are distinct in

their primary DNA and protein sequences from other MLVs, and phylogenetic

analysis based upon these new data recapitulates the previously env and

LTR results, again placing HEMV in a relatively central position.  Studies are

underway to identify HEMV in other mouse species, to determine if the entire

provirus is competent for replication, and to define the receptor used that

provides this virus with its unique ecotropic host range.