The rapid accumulation of NS4 in the cytoplasm as early as 4 hours post-infection suggests that this protein plays an early role in the virus replication cycle. At 72 hours post-infection NS4 was absent from the nucleus which could be the consequence of changes affecting the nucleus and the integrity of the nuclear membrane. The presence of the NS4 in the plasma membrane late in infection suggests that it may play a role, alongside NS1 and NS3, in virus exit. Further co-localisation studies will be carried out to assess NS4 interactions with other viral or cellular protein components.  Geographic Distribution and Risk Factors of the Initial Adult Hospitalized Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in Mainland China BACKGROUND: As of 31(st) March 2010, more than 127,000 confirmed cases of 2009 pandemic influenza A (H1N1), including 800 deaths, were reported in mainland China. The distribution and characteristics of the confirmed cases in the initial phase of this pandemic in this country are largely unknown. The present study aimed to characterize the geographic distribution and patient characteristics of H1N1 infection in the 2009 pandemic as well as to identify potential risk factors associated with adverse patient outcome in China, through retrospective analyses of 885 hospitalized cases with confirmed H1N1 infection. METHODOLOGY/PRINCIPAL FINDINGS: The proportional hazards model was employed to detect risk factors for adverse outcome; the geo-statistical maps were used to characterize the distribution of all 2668 confirmed H1N1 patients throughout mainland China. The number of new cases increased slowly in May, 2009, but rapidly between June and August of the year. Confirmed cases were reported in 26 provinces; Beijing, Guangdong, Shanghai, Zhejiang and Fujian were the top five regions of the incidence of the virus infection. After being adjusted for gender, age, chronic pulmonary disease and other general symptoms, delay for more than two days before hospital admission (HR: 0.6; 95%CI: 0.5–0.7) and delayed onset of the H1N1-specific respiratory symptoms (HR: 0.3; 95%CI: 0.2–0.4) were associated with adverse patient outcome. CONCLUSIONS/SIGNIFICANCE: The 2009 pandemic influenza A affected east and southeast coastal provinces and most populous cities more severely than other regions in mainland China due to higher risk of high level traffic-, high population density-, and high population mobility-associated H1N1 transmission.The clinical symptoms were mild in the initial phase of infection. Delayed hospital admission and delayed appearance of respiratory symptoms were among the major risk factors for poor patient outcome. These findings may have significant implications in the future pandemic preparedness and response. The 2009 pandemic influenza A (H1N1) was first reported in Mexico and then rapidly spread around the world, unfortunately due to the 'convenience' of airplane-based modern transportation system. On 11 th June 2009, the World Health Organization (WHO) raised the warning level to the sixth phase, indicating that the episode of influenza had entered a pandemic stage [1] . As of 11 th April 2010, more than 214 countries and territories or communities had reported laboratory-confirmed cases of 2009 H1N1, including over 17798 deaths [2] . The first case in mainland china was reported on May 11 th , 2009. The Ministry of Health of the People's Republic of China released Guidelines for H1N1 Influenza Diagnosis and Treatment in the middle of July, 2009 [3] . By March 31 st 2010, more than 127,000 laboratorial confirmed cases including 800 deaths were reported in the country [4] .