In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Input: Consider Input: Interferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh) IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.

Output: Rhesus macaque IFITM3 gene polymorphisms and SIV infection


Input: Consider Input: The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.

Output: Pharmacologic inhibition of host Phosphodiesterase-4 improves isoniazid-Mediated clearance of Mycobacterium tuberculosis


Input: Consider Input: We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200-49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored. C yclospora cayetanensis is a protozoan parasite that may cause gastroenteritis with prolonged, intermittent diarrhea in humans. Characterization and magnitudes of risk factors associated with food and water consumption are unclear because the dose-response relationship and other host-parasite factors for infection with Cyclospora are unknown. To characterize infectivity, we performed a study in which inocula of Cyclospora oocysts were administered to human volunteers. Stool samples containing high concentrations of Cyclospora oocysts and serum specimens were collected from persons with cyclosporiasis in Haiti and the United States. Informed consent was obtained from persons providing the specimens. The Centers for Disease Control and Prevention (CDC) institutional review board (IRB) reviewed specimen collection, informed consent, and patient counseling procedures. Stool specimens were homogenized with water and sieved through cheesecloth. Since Cyclospora oocysts must form sporocysts outside the human host before becoming infectious, the filtrate was resuspended in potassium dichromate (2.5%) and shaken for about 3 weeks at room temperature to induce sporulation. After sporulation (67%-94% of oocysts sporulated), samples were stored at room temperature until further processing (2-3 months). Suspensions with the DISPATCHES 726 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 4,


Output: Human Challenge Pilot Study with Cyclospora cayetanensis