Infected Deer Mice Research Articles

SARS-CoV-2 infects multiple species of North American deer mice and causes clinical disease in the California mouse

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease-19 (COVID-19), emerged in late 2019 in Wuhan, China and its rapid global spread has resulted in millions of deaths. An important public health consideration is the potential for SARS-CoV-2 to establish endemicity in secondary animal reservoirs outside of Asia or acquire adaptations that result in new variants with the ability to evade the immune response and reinfect the human population. Previous work has shown that North American deer mice (Peromyscus maniculatus) are susceptible and can transmit SARS-CoV-2 to naïve conspecifics, indicating its potential to serve as a wildlife reservoir for SARS-CoV-2 in North America. In this study, we report experimental SARS-CoV-2 susceptibility of two additional subspecies of the North American deer mouse and two additional deer mouse species, with infectious virus and viral RNA present in oral swabs and lung tissue of infected deer mice and neutralizing antibodies present at 15 days post-challenge. Moreover, some of one species, the California mouse (P. californicus) developed clinical disease, including one that required humane euthanasia. California mice often develop spontaneous liver disease, which may serve as a comorbidity for SARS-CoV-2 severity. The results of this study suggest broad susceptibility of rodents in the genus Peromyscus and further emphasize the potential of SARS-CoV-2 to infect a wide array of North American rodents.

Increased Ifng and Il10 Expression Correlate with Disease in Rodent Models Experimentally Infected with Modoc Virus.

Flaviviruses present an ongoing threat to global public health, although the factors that contribute to the disease remain incompletely understood. We examined an acute Modoc virus (MODV) infection of two rodent models. Viral RNA was detected in the kidneys, spleen, liver, brain, urine, and sera of experimentally infected deer mice, a reservoir host of MODV, and Syrian hamsters, a known disease model. As expected, clinical outcomes differed between species, and the levels of viral RNA recovered from various tissues demonstrated signs of differential replication and tissue tropism. Multivariate analysis indicated significance in the profile of expressed genes between species when analyzed across tissues and over time (p = 0.02). Between-subject effects with corrected models revealed a significance specific to the expression of Ifng (p = 0.01). the expression of Ifng was elevated in hamsters as compared to deer mice in brain tissues at all timepoints. As the over-expression of Ifng has been shown to correlate with decreased vascular integrity, the findings presented here offer a potential mechanism for viral dissemination into the CNS. The expression of IL10 also differed significantly between species at certain timepoints in brain tissues; however, it is uncertain how increased expression of this cytokine may influence the outcome of MODV-induced pathology.

Oral Vaccination With Recombinant Vesicular Stomatitis Virus Expressing Sin Nombre Virus Glycoprotein Prevents Sin Nombre Virus Transmission in Deer Mice.

Sin Nombre virus (SNV) is the major cause of hantavirus cardiopulmonary syndrome (HCPS) in North America, a severe respiratory disease with a high fatality rate. SNV is carried by Peromyscus maniculatus, or deer mice, and human infection occurs following inhalation of aerosolized virus in mouse excreta or secreta, often in peri-domestic settings. Currently there are no FDA approved vaccines or therapeutics for SNV or any other hantaviruses, therefore prevention of infection is an important means of reducing the disease burden of HCPS. One approach for preventing HCPS cases is to prevent the spread of the virus amongst the rodent reservoir population through bait vaccination. However, bait style vaccines for rodent-borne viruses have not been employed in the field, unlike those targeting larger species. Here we utilized a recombinant vesicular stomatitis virus expressing SNV glycoprotein precursor (rVSVΔG/SNVGPC) in an attempt to prevent SNV transmission. Vaccination of deer mice with rVSVΔG/SNVGPC was able to reduce viral RNA copy numbers in the blood and lungs of directly infected animals. More importantly, vaccination, either intramuscularly or orally, significantly reduced the number of transmission events in a SNV transmission model compared with control animals. This provides a proof-of-concept in which oral vaccination of deer mice results in protection against acquiring the virus following direct contact with infected deer mice. Further development of bait style vaccines for SNV or other rodent-borne viruses could provide an effective means of reducing disease burden.

Development and Characterization of a Sin Nombre Virus Transmission Model in Peromyscus maniculatus.

In North America, Sin Nombre virus (SNV) is the main cause of hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35–40%. SNV is a zoonotic pathogen carried by deer mice (Peromyscus maniculatus), and few studies have been performed examining its transmission in deer mouse populations. Studying SNV and other hantaviruses can be difficult due to the need to propagate the virus in vivo for subsequent experiments. We show that when compared with standard intramuscular infection, the intraperitoneal infection of deer mice can be as effective in producing SNV stocks with a high viral RNA copy number, and this method of infection provides a more reproducible infection model. Furthermore, the age and sex of the infected deer mice have little effect on viral replication and shedding. We also describe a reliable model of direct experimental SNV transmission. We examined the transmission of SNV between deer mice and found that direct contact between deer mice is the main driver of SNV transmission rather than exposure to contaminated excreta/secreta, which is thought to be the main driver of transmission of the virus to humans. Furthermore, increases in heat shock responses or testosterone levels in SNV-infected deer mice do not increase the replication, shedding, or rate of transmission. Here, we have demonstrated a model for the transmission of SNV between deer mice, the natural rodent reservoir for the virus. The use of this model will have important implications for further examining SNV transmission and in developing strategies for the prevention of SNV infection in deer mouse populations.

Quantitative Shedding of Multiple Genotypes of Cryptosporidium and Giardia by Deer Mice (Peromyscus maniculatus) in a Major Agricultural Region on the California Central Coast

Deer mice (Peromyscus maniculatus) are abundant and widely distributed rodents in North America that occupy diverse habitats, including agricultural landscapes. Giardia and Cryptosporidium are common parasites in wildlife including deer mice, which may play a role in on-farm contamination of produce. An important step in assessing the risk of produce contamination by Cryptosporidium and Giardia shed by deer mice is to determine the prevalence, levels, and genotypes of (oo)cysts in mouse feces. A total of 63 (30.3%) and 53 (25.5%) of 208 deer mice trapped on 12 farms on the California Central Coast were positive for Cryptosporidium and Giardia, respectively. Of these mice, 41 (19.7%) contained both parasites. The odds of Cryptosporidium shedding were 2.5 to 5 times higher for mice trapped in autumn than for mice trapped in summer or spring. Female mice had a higher prevalence and two- to threefold higher levels of Cryptosporidium and Giardia compared with male mice. Female adults and female juveniles had the highest rates of contamination of the environment with Cryptosporidium and Giardia, respectively. We estimated that 20 infected deer mice inhabiting 1 ha of a typical leafy green produce farm in the study region could shed approximately 5.3 × 108 Cryptosporidium and 10.5 × 108 Giardia, respectively, per day into the environment. The small-subunit rRNA gene loci from a subset of protozoan isolates were sequenced and compared with existing sequences in GenBank. Multiple genotypes of Cryptosporidium and Giardia were found, and BLAST analyses suggest that Giardia and the majority of Cryptosporidium genotypes in deer mice circulate within various rodent populations, but some Cryptosporidium isolates possess zoonotic potential.

Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus).

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse (Peromyscus maniculatus), the natural reservoir host of Sin Nombre virus (SNV), and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7–14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir.

Hantavirus pulmonary syndrome in Canada: An overview of clinical features, diagnostics, epidemiology and prevention.

Hantavirus pulmonary syndrome is a disease caused by the inhalation of excreta from infected deer mice. In Canada, the majority of hantavirus pulmonary syndrome cases occur in the western provinces of British Columbia, Alberta, Saskatchewan and Manitoba and the primary cause of the illness is the Sin Nombre virus. Only one case of hantavirus pulmonary syndrome has been documented in eastern Canada (Québec); however, Sin Nombre virus-infected deer mice have been identified across the country. Although cases are rare (yearly case numbers range from zero to 13 and the total number of confirmed cases in Canada now total 109), the mortality rate among infected individuals is approximately 30%. The majority of cases occur in the spring and early summer indicating seasonally-associated risk factors for viral exposure. In 2013 and 2014, a substantial increase in the number of hantavirus pulmonary syndrome cases was identified; however the cause remains unclear. No antivirals or vaccines are currently available and treatment is supportive. Public education, rodent control and the use of personal protective measures are key to avoid infections in at-risk populations.

Predominant Th2 cytokine gene expression in lymph node cell cultures from Andes virus-infected deer mice (Peromyscus maniculatus) (P6316)

Abstract Deer mice (Peromyscus maniculatus) are the principal reservoir hosts of Sin Nombre virus (SNV), while long-tailed pygmy rice rats (Oligoryzomys longicaudatus) are the principal reservoir hosts of Andes virus (ANDV). These viruses cause the great majority of hantavirus cardiopulmonary syndrome cases in North and South America. The disease in humans is principally an inflammatory immunopathology that results in a pronounced capillary leak syndrome with a 36% fatality rate due to cardiogenic shock. In contrast, infection of rodent reservoirs with their hantaviruses results in life-long persistence, without signs of disease, that appears to be mediated by regulatory T cells. Deer mice are experimentally susceptible to ANDV; however, they clear infection within 56 days. We infected deer mice with SNV or ANDV for 14 days and examined the immune responses to each virus. Lymph node cells from infected deer mice were harvested and cultured with viral antigens to examine expression of 94 immune-related genes by real-time PCR. We found that most of the same genes were expressed in both SNV- and ANDV-infected deer mice; however, the magnitude of gene expression, particularly Th2 genes, were significantly greater in lymph node cells from ANDV-infected deer mice. Together, these results suggest a quantitative effect occurs in the host response to a reservoir hantavirus (SNV) compared to a nonreservoir hantavirus (ANDV) and is associated with persistence or clearance.

Experimental Andes Virus Infection in Deer Mice: Characteristics of Infection and Clearance in a Heterologous Rodent Host

New World hantaviruses can cause hantavirus cardiopulmonary syndrome with high mortality in humans. Distinct virus species are hosted by specific rodent reservoirs, which also serve as the vectors. Although regional spillover has been documented, it is unknown whether rodent reservoirs are competent for infection by hantaviruses that are geographically separated, and known to have related, but distinct rodent reservoir hosts. We show that Andes virus (ANDV) of South America, carried by the long tailed pygmy rice rat (Oligoryzomys longicaudatus), infects and replicates in vitro and in vivo in the deer mouse (Peromyscus maniculatus), the reservoir host of Sin Nombre virus (SNV), found in North America. In experimentally infected deer mice, viral RNA was detected in the blood, lung, heart and spleen, but virus was cleared by 56 days post inoculation (dpi). All of the inoculated deer mice mounted a humoral immune response by 14 dpi, and produced measurable amounts of neutralizing antibodies by 21 dpi. An up-regulation of Ccl3, Ccl4, Ccl5, and Tgfb, a strong CD4+ T-cell response, and down-regulation of Il17, Il21 and Il23 occurred during infection. Infection was transient with an absence of clinical signs or histopathological changes. This is the first evidence that ANDV asymptomatically infects, and is immunogenic in deer mice, a non-natural host species of ANDV. Comparing the immune response in this model to that of the immune response in the natural hosts upon infection with their co-adapted hantaviruses may help clarify the mechanisms governing persistent infection in the natural hosts of hantaviruses.

Kinetics of Immune Responses in Deer Mice Experimentally Infected with Sin Nombre Virus

Deer mice are the principal reservoir hosts of Sin Nombre virus, the etiologic agent of most hantavirus cardiopulmonary syndrome cases in North America. Infection of deer mice results in persistence without conspicuous pathology, and most, if not all, infected mice remain infected for life, with periods of viral shedding. The kinetics of viral load, histopathology, virus distribution, and immune gene expression in deer mice were examined. Viral antigen was detected as early as 5 days postinfection and peaked on day 15 in the lungs, hearts, kidneys, and livers. Viral RNA levels varied substantially but peaked on day 15 in the lungs and heart, and antinucleocapsid IgG antibodies appeared in some animals on day 10, but a strong neutralizing antibody response failed to develop during the 20-day experiment. No clinical signs of disease were observed in any of the infected deer mice. Most genes were repressed on day 2, suggesting a typical early downregulation of gene expression often observed in viral infections. Several chemokine and cytokine genes were elevated, and markers of a T cell response occurred but then declined days later. Splenic transforming growth factor beta (TGF-β) expression was elevated early in infection, declined, and then was elevated again late in infection. Together, these data suggest that a subtle immune response that fails to clear the virus occurs in deer mice.

Using MODIS satellite imagery to predict hantavirus risk

Aims Sin Nombre virus (SNV), a strain of hantavirus, causes hantavirus pulmonary syndrome (HPS) in humans, a deadly disease with high mortality rate (> 50%). The primary virus host is the deer mouse, and greater abundance of deer mice has been shown to increase the human risk of HPS. Our aim is to identify and compare vegetation indices and associated time lags for predicting hantavirus risk using remotely sensed imagery. Location Utah, USA. Methods A 5-year time-series of moderate-resolution imaging spectroradiometer (MODIS) satellite imagery and corresponding field data was utilized to compare various vegetation indices that measure productivity with the goal of indirectly estimating mouse abundance and SNV prevalence. Relationships between the vegetation indices and deer mouse density, SNV prevalence and the number of infected deer mice at various time lags were examined to assess which indices and associated time lags might be valuable in predicting SNV outbreaks. Results The results reveal varying levels of positive correlation between the vegetation indices and deer mouse density as well as the number of infected deer mice. Among the vegetation indices, the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) produced the highest correlations with deer mouse density and the number of infected deer mice using a time lag of 1.0 to 1.3 years for May and June imagery. Main conclusions This study demonstrates the potential for using MODIS time-series satellite imagery in estimating deer mouse abundance and predicting hantavirus risk. The 1-year time lag provides a great opportunity to apply satellite imagery to predict upcoming SNV outbreaks, allowing preventive strategies to be adopted. Analysis of different predictive indices and lags could also be valuable in identifying the time windows for data collection for practical uses in monitoring rodent abundance and subsequent disease risk to humans.

The Relative Abundance of Deer Mice with Antibody to Sin Nombre Virus Corresponds to the Occurrence of Hantavirus Pulmonary Syndrome in Nearby Humans

Sin Nombre virus (SNV) is the principal cause of hantavirus pulmonary syndrome (HPS) in the United States and deer mice (Peromyscus maniculatus) are its principal rodent host, and thus the natural cycle of the virus is related to the occurrence of HPS. Prevalence of rodent infection appears to be associated with fluctuations in deer mouse populations and, indirectly, with timing and amount of precipitation, a complex of biologic events. Given that rodent population abundances fluctuate, often acutely, it is not unreasonable to assume a direct correlation between the numbers of infected rodents and the number of human infections, unless confounding factors are involved. During a 13-year longitudinal study at a site in southwestern Colorado, we accumulated data regarding deer mice and antibody to SNV and therefore had the opportunity to compare dynamics of deer mouse populations, seroprevalence of antibody to SNV in the rodents, and numbers of HPS cases in Durango and in the State of Colorado as a whole. If abundances of deer mouse populations are directly correlated with occurrence of HPS, it is reasonable to assume that low densities of deer mice and low prevalences of antibody to SNV would lead to fewer human cases than would high densities and high prevalences. Our results substantiate such an assumption and suggest that the risk of acquisition of HPS is likely related to both high numbers of infected deer mice and human activities, rather than being strictly related to prevalence of SNV in the host rodent.

NATURAL HISTORY OF SIN NOMBRE VIRUS INFECTION IN DEER MICE IN URBAN PARKS IN OREGON

Sin Nombre virus (SNV), one of at least 45 hantaviruses described worldwide, is hosted by the deer mouse, Peromyscus maniculatus, a common species throughout most of North America. Herein, we describe general life-history characteristics of deer mice and the ways in which these factors relate to the incidence of SNV infections among populations of this host species in and around Portland, Oregon. In total, 3,175 deer mice were captured from October 2002 to September 2005. Transmission of SNV appears to be associated with male breeding behaviors, as more males and adults were infected than expected by capture rate; spring and summer had the highest infection prevalence, as well as scrotal male captures. Wounding rates between infected and uninfected deer mice were not different in any age or sex class. Capture rates were significantly and positively related to the interaction of temperature departure from normal, total precipitation, and number of clear days from two seasons previous (P=0.029), while infection prevalence was significantly and negatively related to the capture rate of juveniles from two seasons previous (P=0.029).

SEASONAL DISPERSAL PATTERNS OF SYLVAN DEER MICE (PEROMYSCUS MANICULATUS) WITHIN MONTANA RANGELANDS

We examined seasonal dispersal patterns and timing of new infections of Sin Nombre virus (SNV), as determined by recent acquisition of antibodies (seroconversion), in deer mice (Peromyscus maniculatus) at two Montana rangeland study sites over three years, 2004-2007. One study site was located in grassland habitat, and the other was located in shrub-steppe. In Montana, both of these habitats are commonly associated with peridomestic environments (in and around buildings). Peridomestic environments are where most reported human cases of hantavirus pulmonary syndrome (HPS) likely originate. Furthermore, deer mice dispersing from sylvan habitats colonize peridomestic environments. Thus, a thorough understanding of deer mouse dispersal is needed to help predict when humans are most at risk for exposure to SNV. We trapped mice at each study site twice a month, accumulating 85,200 trap nights of effort and capturing 6,185 individual deer mice a total of 22,654 times. We documented 980 dispersing individuals over 3 yr. We found positive correlations between the number of dispersing mice and number captured at each site, but there were no statistically significant seasonal differences in the number of dispersing mice. However, we did find a spring/summer bias in mice that seroconverted and dispersed, suggesting that recently infected deer mice are most likely to enter settings where humans may be exposed to SNV during spring and summer.

Genomic organization and phylogenetic utility of deer mouse (Peromyscus maniculatus) lymphotoxin-alpha and lymphotoxin-beta

BackgroundDeer mice (Peromyscus maniculatus) are among the most common mammals in North America and are important reservoirs of several human pathogens, including Sin Nombre hantavirus (SNV). SNV can establish a life-long apathogenic infection in deer mice, which can shed virus in excrement for transmission to humans. Patients that die from hantavirus cardiopulmonary syndrome (HCPS) have been found to express several proinflammatory cytokines, including lymphotoxin (LT), in the lungs. It is thought that these cytokines contribute to the pathogenesis of HCPS. LT is not expressed by virus-specific CD4+ T cells from infected deer mice, suggesting a limited role for this pathway in reservoir responses to hantaviruses.ResultsWe have cloned the genes encoding deer mouse LTα and LTβ and have found them to be highly similar to orthologous rodent sequences but with some differences in promoters elements. The phylogenetic analyses performed on the LTα, LTβ, and combined data sets yielded a strongly-supported sister-group relationship between the two murines (the house mouse and the rat). The deer mouse, a sigmodontine, appeared as the sister group to the murine clade in all of the analyses. High bootstrap values characterized the grouping of murids.ConclusionNo conspicuous differences compared to other species are present in the predicted amino acid sequences of LTα or LTβ; however, some promoter differences were noted in LTβ. Although more extensive taxonomic sampling is required to confirm the results of our analyses, the preliminary findings indicate that both genes (analyzed both separately and in combination) hold potential for resolving relationships among rodents and other mammals at the subfamily level.

Sin Nombre Virus Shedding Patterns in Naturally Infected Deer Mice (Peromyscus maniculatus) in Relation to Duration of Infection

A 2-year capture-mark-recapture study was conducted in southern Manitoba, Canada, to test for an association between the duration of Sin Nombre virus (SNV) infection in deer mice (Peromyscus maniculatus) and virus shedding. Hantavirus-specific IgG antibodies were detected in 22.2% of captured deer mice, and recently infected deer mice were identified based on the detection of low-avidity IgG antibodies. SNV RNA was detected in blood samples from the majority of seropositive deer mice with no significant difference in the association of SNV RNA between the low- and high-avidity groups (57.8% and 52.1%, respectively). A small subset of seropositive mice (11.6%) had detectable SNV RNA in oropharyngeal fluids (OPF) or urine. A greater proportion of deer mice with low-avidity antibodies had SNV RNA in OPF or urine compared with rodents with high-avidity antibodies (21% versus 6.8%, respectively). This is the first study of naturally infected deer mice to provide evidence that recently infected mice are more likely to shed SNV and thus might represent a greater risk of human infection.

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus.

Hantavirus cardiopulmonary syndrome is a zoonotic illness associated with a systemic inflammatory immune response, capillary leak, noncardiogenic pulmonary edema, and shock in humans. Cytokines, including TNF, IFN-gamma, and lymphotoxin, are thought to contribute to its pathogenesis. In contrast, infected rodent reservoirs of hantaviruses experience few or no pathologic changes and the host rodent can remain persistently infected for life. Generally, it is unknown why such dichotomous immune responses occur between humans and reservoir hosts. Thus, we examined CD4(+) T cell responses from one such reservoir, the deer mouse (Peromyscus maniculatus), infected with Sin Nombre virus. Proliferation responses to viral nucleocapsid antigen were relatively weak in T cells isolated from deer mice, regardless of acute or persistent infection. The T cells from acutely infected deer mice synthesized a broad spectrum of cytokines, including IFN-gamma, IL-4, IL-5, and TGF-beta(1), but not TNF, lymphotoxin, or IL-17. However, in T cells from persistently infected deer mice, only TGF-beta(1) was expressed by all lines, whereas some expressed reduced levels of IFN-gamma or IL-5. The Forkhead box P3 transcription factor, a marker of some regulatory T cells, was expressed by most of these cells. Collectively, these data suggest that TGF-beta(1)-expressing regulatory T cells may play an important role in limiting immunopathology in the natural reservoir host, but this response may interfere with viral clearance. Such a response may have arisen as a mutually beneficial coadaptive evolutionary event between hantaviruses and their rodent reservoirs, so as to limit disease while also allowing the virus to persist.

PERSISTENTLY HIGHEST RISK AREAS FOR HANTAVIRUS PULMONARY SYNDROME: POTENTIAL SITES FOR REFUGIA

Interannual variation in the number of cases of human disease caused by hantaviruses in North America has been hypothesized to reflect environmental changes that influence rodent reservoir populations. This hypothesis postulates that when cases are rare reservoir populations are geographically restricted in patches of suitable habitat. Identifying these sites, which is needed to test the hypothesis, has proven to be a challenge. Satellite imagery of the U.S. Southwest has shown associations among the likelihood of human hantaviral disease and increases in the rodent populations, as well as increased prevalence of Sin Nombre virus (SNV) in rodent populations. In this study we characterize local areas that had environmental signatures that persisted as predicted highest risk sites for human disease through much of the 1990s. These areas represent a small percentage (0.3%) of the region. Exploratory analyses indicate that these areas were not randomly distributed, but were associated with certain landscape characteristics. Characteristics of elevation, slope, aspect, and land cover were associated with persistent high risk. Using multivariate Poisson regression to control for confounding effects, sites with deciduous- or mixed-forest land cover on moderate to steep slopes (>5 degrees) above 2130 m elevation were associated with increasing numbers of years at highest risk. These are candidate locations for refugia. Sites associated with cleared ground or shrubland were less often associated with high risk compared to reference conditions. The seasonal patterns of vegetation growth in persistently high-risk areas were compared to matched locations using MODIS (moderate resolution imaging spectroradiometer) NDVI (normalized difference vegetation index) during a time of a severe drought in the region from 2002 to 2004. Despite the drought and regardless of land cover, the NDVI in persistently highest risk areas had an early onset, with significantly higher levels of green vegetation that lasted longer than at comparable sites. These observations identify locations that can be monitored for the abundance of P. maniculatus and presence of SNV. If these sites are refugia, we predict they will be occupied by infected deer mice when other monitored sites are unoccupied.

USE OF IgG AVIDITY TO INDIRECTLY MONITOR EPIZOOTIC TRANSMISSION OF SIN NOMBRE VIRUS IN DEER MICE (PEROMYSCUS MANICULATUS)

An IgG avidity assay was developed to differentiate deer mice that had recently acquired Sin Nombre virus (SNV) from those that were infected in the distant past. Using this procedure, low avidity antibodies were predominantly detected in experimentally infected deer mice (89.5%) within the first 30 days post-inoculation. The assay was then applied to sera from naturally infected deer mice collected during a field investigation associated with a cluster of hantavirus pulmonary syndrome cases. A higher proportion of seropositive mice collected during the outbreak had serum with low avidity antibodies (16.7%) when compared with mice trapped four months later (5.7%). Sin Nombre virus RNA was detectable in blood in a similar fraction of low- (45%) and high- (38.7%) avidity groups. Non-adult mice were more likely to contain low-avidity antibodies (44.4%) than were adults (9.6%). Our results indicate that the IgG avidity assay shows promise as a tool to better characterize epizootic intensity and to identify factors involved in SNV transmission.

Research Article: Genomic organization of deer mouse (Peromyscus maniculatus) tumor necrosis factor

Abstract Tumor necrosis factor (TNF) is a mediator of inflammation during immune responses and is produced by activated macrophages and T cells. It is synthesized as a membrane-bound homotrimer that is released from activated cells. Its functions are to inhibit viral replication, cause capillary leakage, induce cell apoptosis, and to recruit other immune cells to the infected area. Many humans infected with Sin Nombre (SN) virus develop an inflammatory pulmonary immunopathology caused by abundant production of TNF. In contrast, infected deer mice, the natural reservoir of SN virus, exhibit no pathology or inflammation in the lungs. Because of this, it is unlikely that deer mice produce appreciable amounts of TNF in response to SN virus infection. To begin to address this issue, we have cloned and sequenced the Tnf gene of deer mice. We obtained all but the final 9 nucleotides of Tnf and have determined that it is highly conserved with orthologous sequences.