West Nile Disease in New Mexico: The Quest for Nucleic Acid

West Nile virus (WNV) was first detected in New Mexico in 2002, with the first human cases appearing in 2003. Since that time it has become endemic in the region, and as of year-end 2005, 330 New Mexicans had been diagnosed with West Nile Fever or the more severe neuroinvasive disease as reported by the New Mexico Department of Health. An ongoing study at the University of New Mexico has collected interview and physical exam data for these individuals as well as collecting cerebrospinal fluid (CSF) and serum from their period of acute and convalescent illness. While all of these samples have been tested to determine WNV IgM seropositivity, none of them have been characterized by the use of nucleic acid amplification test (NAT). The purpose of this study is to characterize this sample set using Real-Time reverse transcriptase polymerase chainreaction (RT-PCR), an extremely sensitive NAT. The serum and CSF archived collection at UNM represents one of the most comprehensive and best-characterized sample sets available in the United States. A total of 115 samples, 111 serum and 4 CSF, were analyzed. None of the 115 samples had detectable West Nile nucleic acid

Neutralizing Antibodies and Sin Nombre Virus RNA after Recovery from Hantavirus Cardiopulmonary Syndrome

Patients who later have a mild course of hantavirus cardiopulmonary syndrome (HCPS) are more likely to exhibit a high titer of neutralizing antibodies against Sin Nombre virus (SNV), the etiologic agent of HCPS, at the time of hospital admission. Because administering plasma from patients who have recovered from HCPS to those in the early stages of disease may be an advantageous form of passive immunotherapy, we examined the neutralizing antibody titers of 21 patients who had recovered from SNV infection. Even 1,000 days after admission to the hospital, 6 of 10 patients had titers of 800 or higher, with one sample retaining a titer of 3,200 after more than 1,400 days. None of the convalescent-phase serum samples contained detectable viral RNA. These results confirm that patients retain high titers of neutralizing antibodies long after recovery from SNV infection

Mental Status after West Nile Virus Infection

Mental status after acute West Nile virus infection has not been examined objectively. We compared Telephone Interview for Cognitive Status scores of 116 patients with West Nile fever or West Nile neuroinvasive disease. Mental status was poorer and cognitive complaints more frequent with West Nile neuroinvasive disease (p = 0.005)

Distribution and prevalence of Sin Nombre hantavirus in rodent species in eastern New Mexico.

Orthohantaviruses are diverse zoonotic RNA viruses. Small mammals, such as mice and rats are common chronic, asymptomatic hosts that transmit the virus through their feces and urine. In North America, hantavirus infection primarily causes hantavirus cardiopulmonary syndrome (HCPS), which has a mortality rate of nearly 36%. In the United States of America, New Mexico (NM) is leading the nation in the number of HCPS-reported cases (N = 129). However, no reported cases of HCPS have occurred within eastern NM. In this study, we assessed the prevalence of Sin Nombre virus (SNV) in rodent assemblages across eastern NM, using RT-qPCR. We screened for potential rodent hosts in the region, as well as identified areas that may pose significant infection risk to humans. We captured and collected blood and lung tissues from 738 rodents belonging to 23 species. 167 individuals from 16 different species were positive for SNV RNA by RT-qPCR, including 6 species unreported in the literature: Onychomys leucogaster (Northern grasshopper mouse), Dipodomys merriami (Merriam's kangaroo rat), Dipodomys ordii (Ord's kangaroo rat), Dipodomys spectabilis (Banner-tailed kangaroo rat), Perognathus flavus (Silky pocket mouse), and Chaetodipus hispidus (Hispid pocket mouse). The infection rates did not differ between sexes or rodent families (i.e., Cricetidae vs. Heteromyidae). Generalized linear model showed that disturbed habitat types positively influenced the prevalence of SNV at sites of survey. Overall, the results of this study indicate that many rodent species in east New Mexico have the potential to maintain SNV in the environment, but further research is needed to assess species specific infectivity mechanisms and potential risk to humans

CD74 is highly expressed in human gastric and colon tumors and on isolated epithelial cells.

<p>CD74 mRNA levels measured by qRT PCR are increased in A) human gastric tumor samples and at higher levels in tissues from patients with nodal involvement, B) human colon tumor samples and at higher levels in tissues from patients with nodal involvement, and on epithelial cells isolated from human gastric and colon tumors in C) a representative flow cytometry plot and D) in compiled flow cytometry data from all samples. N = 8 for D and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p

Use of a Novel Detection Tool to Survey Orthohantaviruses in Wild-Caught Rodent Populations

Orthohantaviruses are negative-stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. Old World orthohantaviruses are primarily located throughout Europe and Asia, causing hemorrhagic fever with renal syndrome, and New World orthohantaviruses are found in North, Central, and South America, causing hantavirus cardiopulmonary syndrome (HCPS). In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of HCPS with a fatality rate of ~36%. The primary SNV host reservoir is thought to be the North American deer mouse, Peromyscus maniculatus. However, it has been shown that other species of Peromyscus can carry different orthohantaviruses. Few studies have systemically surveyed which orthohantaviruses may exist in wild-caught rodents or monitored spillover events into additional rodent reservoirs. A method for the rapid detection of orthohantaviruses is needed to screen large collections of rodent samples. Here, we report a pan-orthohantavirus, two-step reverse-transcription quantitative real-time PCR (RT-qPCR) tool designed to detect both Old and New World pathogenic orthohantavirus sequences of the S segment of the genome and validated them using plasmids and authentic viruses. We then performed a screening of wild-caught rodents and identified orthohantaviruses in lung tissue, and we confirmed the findings by Sanger sequencing. Furthermore, we identified new rodent reservoirs that have not been previously reported as orthohantavirus carriers. This novel tool can be used for the efficient and rapid detection of various orthohantaviruses, while uncovering potential new orthohantaviruses and host reservoirs that may otherwise go undetected

Use of a Novel Detection Tool to Survey Orthohantaviruses in Wild-Caught Rodent Populations

Orthohantaviruses are negative-stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. Old World orthohantaviruses are primarily located throughout Europe and Asia, causing hemorrhagic fever with renal syndrome, and New World orthohantaviruses are found in North, Central, and South America, causing hantavirus cardiopulmonary syndrome (HCPS). In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of HCPS with a fatality rate of ~36%. The primary SNV host reservoir is thought to be the North American deer mouse, Peromyscus maniculatus. However, it has been shown that other species of Peromyscus can carry different orthohantaviruses. Few studies have systemically surveyed which orthohantaviruses may exist in wild-caught rodents or monitored spillover events into additional rodent reservoirs. A method for the rapid detection of orthohantaviruses is needed to screen large collections of rodent samples. Here, we report a pan-orthohantavirus, two-step reverse-transcription quantitative real-time PCR (RT-qPCR) tool designed to detect both Old and New World pathogenic orthohantavirus sequences of the S segment of the genome and validated them using plasmids and authentic viruses. We then performed a screening of wild-caught rodents and identified orthohantaviruses in lung tissue, and we confirmed the findings by Sanger sequencing. Furthermore, we identified new rodent reservoirs that have not been previously reported as orthohantavirus carriers. This novel tool can be used for the efficient and rapid detection of various orthohantaviruses, while uncovering potential new orthohantaviruses and host reservoirs that may otherwise go undetected

MIF induces proliferation of gastric and colon carcinoma cells.

<p>Tumor-derived gastric and colon supernatants induced proliferation of N87 and Caco-2 cells, which was decreased upon adding A) anti-MIF neutralizing antibodies or anti-CD74 blocking antibodies. B) Chronic exposure of HS738 or N87 cells with recombinant MIF increased proliferation that was sustained after returning cells to regular media for 8 weeks. N = 8 and the mean ± standard error are shown as the results of duplicated in multiple experiments. *<i>p</i><0.05.</p