Role of cdk9 in the optimization of expression of the genes regulated by ICP22 of herpes simplex virus 1.

ICP22 is a multifunctional herpes simplex virus 1 (HSV-1) regulatory protein that regulates the accumulation of a subset of late (gamma(2)) proteins exemplified by U(L)38, U(L)41, and U(S)11. ICP22 binds the cyclin-dependent kinase 9 (cdk9) but not cdk7, and this complex in conjunction with viral protein kinases phosphorylates the carboxyl terminus of RNA polymerase II (Pol II) in vitro. The primary function of cdk9 and its partners, the cyclin T variants, is in the elongation of RNA transcripts, although functions related to the initiation and processing of transcripts have also been reported. We report two series of experiments designed to probe the role of cdk9 in infected cells. In the first, infected cells were treated with 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB), a specific inhibitor of cdk9. In cells treated with DRB, the major effect was in the accumulation of viral RNAs and proteins regulated by ICP22. The accumulation of alpha, beta, or gamma proteins not regulated by ICP22 was not affected by the drug. The results obtained with DRB were duplicated in cells transfected with small interfering RNA (siRNA) targeting cdk9 mRNAs. Interestingly, DRB and siRNA reduced the levels of ICP22 but not those of other alpha gene products. In addition, cdk9 and ICP22 appeared to colocalize with RNA Pol II in wild-type-virus-infected cells but not in DeltaU(L)13-infected cells. We conclude that cdk9 plays a critical role in the optimization of expression of genes regulated by ICP22 and that one function of cdk9 in HSV-1-infected cells may be to bring ICP22 into the RNA Pol II transcriptional complex.

Timing of influenza epidemics and vaccines in the American tropics, 2002-2008, 2011-2014.

BACKGROUND: Influenza-associated illness results in increased morbidity and mortality in the Americas. These effects can be mitigated with an appropriately chosen and timed influenza vaccination campaign. To provide guidance in choosing the most suitable vaccine formulation and timing of administration, it is necessary to understand the timing of influenza seasonal epidemics. OBJECTIVES: Our main objective was to determine whether influenza occurs in seasonal patterns in the American tropics and when these patterns occurred. METHODS: Publicly available, monthly seasonal influenza data from the Pan American Health Organization and WHO, from countries in the American tropics, were obtained during 2002-2008 and 2011-2014 (excluding unseasonal pandemic activity during 2009-2010). For each country, we calculated the monthly proportion of samples that tested positive for influenza. We applied the monthly proportion data to a logistic regression model for each country. RESULTS: We analyzed 2002-2008 and 2011-2014 influenza surveillance data from the American tropics and identified 13 (81%) of 16 countries with influenza epidemics that, on average, started during May and lasted 4 months. CONCLUSIONS: The majority of countries in the American tropics have seasonal epidemics that start in May. Officials in these countries should consider the impact of vaccinating persons during April with the Southern Hemisphere formulation.