Global mRNA Degradation during Lytic Gammaherpesvirus Infection Contributes to Establishment of Viral Latency

During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3′ end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68) SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment

Polynomial cycles in certain local domains

1. Let R be a domain and f ∈ R[X] a polynomial. A k-tuple $x₀,x₁,...,x_{k-1}$ of distinct elements of R is called a cycle of f if $f(x_i) = x_{i+1}$ for i=0,1,...,k-2 and $f(x_{k-1}) = x₀$. The number k is called the length of the cycle. A tuple is a cycle in R if it is a cycle for some f ∈ R[X]. It has been shown in [1] that if R is the ring of all algebraic integers in a finite extension K of the rationals, then the possible lengths of cycles of R-polynomials are bounded by the number $7^{7·2^N}$, depending only on the degree N of K. In this note we consider the case when R is a discrete valuation domain of zero characteristic with finite residue field. We shall obtain an upper bound for the possible lengths of cycles in R and in the particular case R=ℤₚ (the ring of p-adic integers) we describe all possible cycle lengths. As a corollary we get an upper bound for cycle lengths in the ring of integers in an algebraic number field, which improves the bound given in [1]. The author is grateful to the referee for his suggestions, which essentially simplified the proof in Subsection 6 and improved the bound for C(p) in Theorem 1 in the case p = 2,3