Upon infection of E. coli, bacteriophage T4 relies on host RNA polymerase (RNAP) to propagate the phage’s genetic material over that of the host. As phage genetic material is produced, infection viability is sustained through the protection of those phage products. Past investigations have shown that wild-type (WT) T4 does not grow on the host strain Rho026. This strain has a mutation within rho, which encodes the main host factor for transcription termination. The inability of WT T4 to grow on Rho026 arises from a decrease in the level of certain middle transcripts, including that of gene 41, the DNA helicase required for T4 DNA replication; a substitution within the T4 early gene goF restores growth and increases the level of gene 41 mRNA. This work initially suggested that goF might encode a transcription anti-termination factor and that the mutant goF is needed to allow growth on the ‘super’ rho mutant strain Rho026. However, other studies revealed that rho026 encodes a protein that is actually a poorer terminator because of a diminished ability to bind RNA. Consequently, the function of GoF during T4 infection and how the goF suppressor mutant promotes growth in Rho026 has still not been elucidated. Using deep blast analyses and the structure predictor program Alphafold2, we have found that GoF belongs to a group of proteins conserved throughout the Myoviridae family. Within T4 there are three orthologs, GoF, MotB.1 and Frd.2. Interestingly, all 3 have predicted SM-fold domains at their N-termini. SM-fold domains have been observed in proteins that bind to RNA. Hfq, the major host RNA chaperone, is one such protein in E. coli. We postulate that GoF (and MotB.1 and Frd.2) may function as T4 RNA chaperones that work as a phage defense against host RNases. We are currently conducting experiments to test this hypothesis. We hope to leverage this mechanistic knowledge to further understand phage-host interactions.