Clinical characteristics and disease burden of respiratory syncytial virus infection among hospitalized adults
Authors: Yoon, Jin Gu; Noh, Ji Yun; Choi, Won Suk; Park, Jin Ju; Suh, Yoo Bin; Song, Joon Young; Cheong, Hee Jin; Kim, Woo Joo
The disease burden of respiratory syncytial virus (RSV) infection in the adult population has not been well characterized compared to children. Investigation of the clinical characteristics and disease burden of adult RSV infection would help to establish public health policy and a future vaccine strategy. We retrospectively collected medical records of hospitalized adult patients who were diagnosed with RSV infection from January 2012 to December 2015 from three tertiary hospitals. Baseline characteristics, clinical outcomes and economic charge during hospitalization were compared by age groups (19-49 years, 50-64 years, and >= 65 years) using Chi-square test. The odds of risk factors of RSV pneumonia were calculated using binary logistic regression. A total of 204 patients from three hospitals were enrolled. Patients who older than 65 years were 132 (64.7%). 118 (57.8%) patients had clinically confirmed pneumonia and 22 (10.8%) died in a hospital. The median medical cost of RSV pneumonia was 2,855.26 USD (interquartile range, 1,561.85-5,379.55) per each admission. Solid cancer (adjusted OR, 3.85; 95% CI, 1.65-9.02, p=0.002) and hematologic malignancy (all patients had pneumonia) were shown to be risk factors for RSV pneumonia. RSV infection in South Korea seemed to have a significant burden among adults as pneumonia, care in the intensive care unit and mortality. Nationwide awareness and further effort to recognize the current burden, prepare specific treatment, and prevent adult RSV infection would be necessary.
TNPO3-Mediated Nuclear Entry of the Rous Sarcoma Virus Gag Protein Is Independent of the Cargo-Binding Domain
JOURNAL OF VIROLOGY
Authors: Rice, Breanna L.; Stake, Matthew S.; Parent, Leslie J.
Retroviral Gag polyproteins orchestrate the assembly and release of nascent virus particles from the plasma membranes of infected cells. Although it was traditionally thought that Gag proteins trafficked directly from the cytosol to the plasma membrane, we discovered that the oncogenic avian alpharetrovirus Rous sarcoma virus (RSV) Gag protein undergoes transient nucleocytoplasmic transport as an intrinsic step in virus assembly. Using a genetic approach in yeast, we identified three karyopherins that engage the two independent nuclear localization signals (NLSs) in Gag. The primary NLS is in the nucleocapsid (NC) domain of Gag and binds directly to importin-alpha, which recruits importin-beta to mediate nuclear entry. The second NLS (TNPO3), which resides in the matrix (MA) domain, is dependent on importin-11 and transportin-3 (TNPO3), which are known as MTR10p and Kap120p in yeast, although it is not clear whether these import factors are independent or additive. The functions of importin-alpha/importin-beta and importin-11 have been verified in avian cells, whereas the role of TNPO3 has not been studied. In this report, we demonstrate that TNPO3 directly binds to Gag and mediates its nuclear entry. To our surprise, this interaction did not require the cargo-binding domain (CBD) of TNPO3, which typically mediates nuclear entry for other binding partners of TNPO3, including SR domain-containing splicing factors and tRNAs that reenter the nucleus. These results suggest that RSV hijacks this host nuclear import pathway using a unique mechanism, potentially allowing other cargo to simultaneously bind TNPO3. IMPORTANCE RSV Gag nuclear entry is facilitated using three distinct host import factors that interact with nuclear localization signals in the Gag MA and NC domains. Here, we show that the MA region is required for nuclear import of Gag through the TNPO3 pathway. Gag nuclear entry does not require the CBD of TNPO3. Understanding the molecular basis for TNPO3-mediated nuclear trafficking of the RSV Gag protein may lead to a deeper appreciation for whether different import factors play distinct roles in retrovirus replication.