Minute virus of mice

MVM uses two transcriptional promoters at map units (mu) 4 and 38 (p4 and p38) and a single polyadenylation site at mu 95 to create 3 major size classes of mRNAs, referred to as R1, R2 and R3, all of which have a short intron sequence between 46–48 mu removed.[5] R1 is produced from p4 and is translated into non-structural protein 1 (NS1). However, in some P4 transcripts a second intron between 10–40 mu is also excised, creating R2 mRNAs that encode NS2 proteins of ~25 kDa. These share 85 amino acids of N-terminal sequence with NS1, and then splice into an alternate reading frame before finally reaching the short central intron where 2 different C-terminal hexapeptides can be added. The R3 transcript produces capsid proteins VP1 and VP2, which requires transcription from the P38 promoter, in contrast to the P4 promoter used for transcripts R1 and R2.[1][6]

NS1 functions as a required replication protein and is known to have helicase activity,[7] ATPase activity [7] and nickase activity.[8] Specifically, the nickase activity is required to resolve replication intermediate telomeres on the right-hand of the genome.[8] NS2 is known to exist in several spliced forms (isoforms) termed NS2-P, -Y and –L due to differences in the C-terminus of the isoforms as a result of alternative splicing.[9] NS2 is known to exist is both the cytoplasm and nucleus as well as in phosphorylated and non-phosphorylated forms.[9] In addition, NS2 is required for efficient infection in its natural murine host, but is dispensable in experimental infection in human cell lines.[9] Although not fully understood, in murine A9 fibroblasts NS2 interacts with nuclear export factor Crm1 resulting in efficient nuclear egress of progeny virions.[9]

MVM induces a DNA damage response (DDR) during infection which is required for effective replication.[10] The ATM pathway is exclusively activated with a primarily Chk2-mediated response.[10] It is not known if viral proteins or active viral replication activate the DDR, but UV-inactivated MVM does not induce a response [10] suggesting that presence of MVM virions or MVM genome alone cannot cause the observed DDR activation.

The Minute virus of Mice is currently the smallest virus that can be easily titrated to high levels; as such it is commercially used as a "worst case" example of a very small virus.[11][12]