PMID- 9573239
OWN - NLM
STAT- MEDLINE
DCOM- 19980527
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 72
IP  - 6
DP  - 1998 Jun
TI  - Mutational and functional analysis of the C-terminal region of the C3H mouse 
      mammary tumor virus superantigen.
PG  - 4746-55
AB  - The mouse mammary tumor virus (MMTV) encodes within the U3 region of the long 
      terminal repeat (LTR) a protein known as the superantigen (Sag). Sag is needed 
      for the efficient transmission of milk-borne virus from the gut to target tissue 
      in the mammary gland. MMTV-infected B cells in the gut express Sag as a type II 
      transmembrane protein that is recognized by the variable region of particular 
      beta chains (Vbeta) of the T-cell receptor (TCR) on the surface of T cells. 
      Recognition of Sag by particular TCRs results in T-cell stimulation, release of 
      cytokines, and amplification of MMTV infection in lymphoid cells that are needed 
      for infection of adolescent mammary tissue. Because the C-terminal 30 to 40 amino 
      acids of Sag are variable and correlate with recognition of particular TCR Vbeta 
      chains, we prepared a series of C-terminal Sag mutations that were introduced 
      into a cloned infectious MMTV provirus. Virus-producing XC rat cells were used 
      for injection of susceptible BALB/c mice, and these mice were monitored for 
      functional Sag activity by the deletion of C3H MMTV Sag-reactive (CD4+ Vbeta14+) 
      T cells. Injected mice also were analyzed for mutant infection and tumor 
      formation in mammary glands as well as milk-borne transmission of MMTV to 
      offspring. Most mutations abrogated Sag function, although one mutation (HPA242) 
      that changed the negative charge of the extreme C terminus to a positive charge 
      created a weaker Sag that slowed the kinetics of Sag-mediated T-cell deletion. 
      Despite the lack of Sag activity, many of the sag mutant viruses were capable of 
      sporadic infections of the mammary glands of injected mice but not of offspring 
      mice, indicating that functional Sag increases the probability of milk-borne MMTV 
      infection. Furthermore, although most viruses encoding nonfunctional Sags were 
      unable to cause mammary tumors, tumors were induced by such viruses carrying 
      mutations in a negative regulatory element that overlaps the sag gene within the 
      LTR, suggesting that loss of Sag function may be compensated, at least partially, 
      by loss of transcriptional suppression in certain tissues. Together these results 
      confirm the importance of Sag for efficient milk-borne transmission and indicate 
      that the entire C-terminal region is needed for complete Sag function.
FAU - Wrona, T J
AU  - Wrona TJ
AD  - Department of Microbiology and Institute for Cellular and Molecular Biology, The 
      University of Texas at Austin, Austin, Texas 78712, USA.
FAU - Lozano, M
AU  - Lozano M
FAU - Binhazim, A A
AU  - Binhazim AA
FAU - Dudley, J P
AU  - Dudley JP
LA  - eng
GR  - T32 CA009583/CA/NCI NIH HHS/United States
GR  - R01 CA34780/CA/NCI NIH HHS/United States
GR  - R01 CA52646/CA/NCI NIH HHS/United States
GR  - T32 CA09583/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA, Viral)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Superantigens)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - DNA Mutational Analysis
MH  - DNA, Viral/*genetics
MH  - Female
MH  - Genes, Viral
MH  - Mammary Tumor Virus, Mouse/*genetics/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C3H
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Rats
MH  - Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology
MH  - Retroviridae Infections/immunology/*virology
MH  - Sequence Alignment
MH  - Superantigens/*genetics/immunology
MH  - Tumor Virus Infections/immunology/*virology
PMC - PMC110007
EDAT- 1998/05/30 00:00
MHDA- 1998/05/30 00:01
PMCR- 1998/06/01
CRDT- 1998/05/30 00:00
PHST- 1998/05/30 00:00 [pubmed]
PHST- 1998/05/30 00:01 [medline]
PHST- 1998/05/30 00:00 [entrez]
PHST- 1998/06/01 00:00 [pmc-release]
AID - 1972 [pii]
AID - 10.1128/JVI.72.6.4746-4755.1998 [doi]
PST - ppublish
SO  - J Virol. 1998 Jun;72(6):4746-55. doi: 10.1128/JVI.72.6.4746-4755.1998.