Encephalomyelitis resulting from virus infection of neurons is a disease that can be fatal or result in permanent disability due to irreversible damage of infected neurons. The immune response to infection can enhance neuronal damage or can control virus replication by noncytolytic mechanisms and thus determine outcome. However, noncytolytic virus clearance results in persistence of viral nucleic acid in the CNS and thus establishes a need for long-term local immune responses to prevent reactivation of infection and progressive disease. Understanding these mechanisms is necessary for development of strategies for treating and preventing neurologic disease due to viral encephalomyelitis. Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008–2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1–3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness. Influenza is the most important respiratory disease in terms of mortality and morbidity. Each year, between 3 and 5 million severe cases and 250,000 to 500,000 deaths due to seasonal influenza are reported worldwide [1, 2] . Cyclic pandemics due to antigenic shifts constitute an important threat [3] as was demonstrated by the swine-origin pandemic of 2009 [4] . Since vaccines for novel influenza virus strains require approximately 6 months to develop and produce [5] , antivirals remain the first line of defense. There are only two classes of antivirals approved for treatment of influenza [6] . The adamantanes, such as amantadine and rimantadine, are ineffective against B-type viruses [7] and have recently become ineffective against most A/H3N2 and some A/H1N1 viruses due to a mutation in the M2 gene [8] . The neuraminidase inhibitors (NAI), which include zanamivir and oseltamivir, were approved a decade ago and have shown excellent activity against all influenza A subtypes and B viruses [9] . A recent rapid increase in resistance to oseltamivir, however, has become a cause for concern.