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Superantigens and retroviral infection:
insights from mouse mammary tumor virus
Werner Held, Hans Acha-Orbea, H. Robson
MacDonald and Gary A. Waanders
Superanttgens reduce :. t%orous immune response by stimulating T cells
that express parucular T-cell receptor VI~ chains. Mouse mammary tumo;
virus ts a nulk-transnutted retro',trus that encodes such a superanttgen.
Paradoxwall); as d~scussed by Werner Held and colleagues, the stro;;g
superanttgen-induced ,mmune response permits the survival of the virus
via T-cell dependent clonal expansion of infected B cells.
Mouse mammary tumor virus ~MMTV), a rephcatlon-
competent B-type retrovlrus, was ~JlSCovered more than
50 years ago as a mdk-borne "enuty' that Induces
mammao carcinomas in mice I The predominant cell
t3.pe permlsswe for efficient replication of MMTV is
the alveolar eptthehal cell of the mammary gland
(revJewed in Ref. 2). During lactation, the expression
of MMTV markedly increases under the mflaence of
steroid hormones. This property largely determines the
life cycle of the virus, whereby MMTV IS secreted m
mothers' mdk and Is transmitted to the offspring,
probably through the gut epithelium. Infectloo of the
mammary gland requires a functional immune s)~-rem~
and it Is now known that the immune system pla), a
central role :n the MMTV hfe cycle.
The long latency period m the development uf mam-
mary tumors after MMTV infection suggests that
MMTV does not contain an oncogene. Instead, upon
'~f~uon of ma,amary epithelial cells, tumors arise as
the result of the integration of provirus into the
genome, m the proximity of either the rot-1 and mr-2
genes or other, as yet undefined, genes. This msertion
event leads to gene actwauon l,ta enhancer activity of
the glucocorttcoLd-response element in the MMTV
':,ng terminal repeat (LTR) (Ref. 4). In addmon, infec-
tious MMTV occasionally integrates m germ cells, to
the extent that MMTV-related sequences are present m
the germhne of all inbred strains of mice and most
wild mice. Many germ-hne transmitted MMTV loci
(Mtv) have now been identified, with most mouse
strams harboring from two to eight distinct provlral
integrations 5.
MMTV encodes a superantigen
The MMTV genome, like that of other retrowruses,
encodes the core proteins (gag), reverse transcriptase
(pol) and the envelope proteins (env) (Fig. 1). After
reverse transcription repeated sequences known as
LTRs are found at the 3' ,,nd 5' ends. It has been
known for some time that the YLTR of MMTV
© 1994. Elsevier ~,clenLeLid 0167-5699/94/$07 fl0
;.,.,unotogy Today 1 8 4 Vo;. !5 No. 4 1994