Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice.

The 1918 influenza pandemic caused over 40 million deaths worldwide, with 675,000 deaths in the United States alone. Studies in several experimental animal models showed that 1918 influenza virus infection resulted in severe lung pathology associated with dysregulated immune and cell death responses. To determine if reactive oxygen species produced by host inflammatory responses play a central role in promoting severity of lung pathology, we treated 1918 influenza virus-infected mice with the catalytic catalase/superoxide dismutase mimetic, salen-manganese complex EUK-207 beginning 3 days postinfection.

Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice.

Highly pathogenic H5N1 influenza shares the same neuraminidase (NA) subtype with the 2009 pandemic (H1N1pdm09), and cross-reactive NA immunity might protect against or mitigate lethal H5N1 infection. In this study, mice were either infected with a sublethal dose of H1N1pdm09 or were vaccinated and boosted with virus-like particles (VLP) consisting of the NA and matrix proteins, standardized by NA activity and administered intranasally, and were then challenged with a lethal dose of HPAI H5N1 virus. Mice previously infected with H1N1pdm09 survived H5N1 challenge with no detectable virus or respiratory tract pathology on day 4.

Obese mice have increased morbidity and mortality compared to non-obese mice during infection with the 2009 pandemic H1N1 influenza virus.

Background: Obesity has been identified as an independent risk factor for severe or fatal infection with 2009 pandemic H1N1 influenza (2009 pH1N1), but was not previously recognized for previous pandemic or seasonal influenza infections.

Objectives: Our aim was to evaluate the role of obesity as an independent risk factor for severity of infection with 2009 pH1N1, seasonal H1N1, or a pathogenic H1N1 influenza virus.

Methods: Diet-induced obese (DIO) and their non-obese, age-matched control counterparts were inoculated with a 2009 pH1N1, A/California/04/2009 (CA/09), current seasonal H1N1, A/NY/312/2001 (NY312), or highly pathogenic 1918-like H1N1, A/Iowa/Swine/1931 (Sw31), virus.

Immunization with 1976 swine H1N1- or 2009 pandemic H1N1-inactivated vaccines protects mice from a lethal 1918 influenza infection.

Background: Zoonotic infections with H1N1 influenza viruses that evolved initially from the 1918 virus (1918) and adapted to swine threatened a pandemic in 1976 (1976 swH1N1) and a novel reassortant H1N1 virus caused a pandemic in 2009-2010 (2009 pH1N1). Epidemiological and laboratory animal studies show that protection from severe 2009 pH1N1 infection is conferred by vaccination or prior infection with 1976 swH1N1 or 1918.

Objectives: Our aim was to demonstrate cross-protection by immunization with 2009 pH1N1 or 1976 swH1N1 vaccines following a lethal challenge with 1918.

Estrogen and progesterone affect responses to malaria infection in female C57BL/6 mice.

Background: Previous data from our laboratory suggest that gonadally intact C57BL/6 male mice are more likely than their female counterparts to die from Plasmodium chabaudi infection, to recover more slowly from weight loss and hematocrit loss, and to have reduced interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) responses. Removal of the ovaries, and hence, the primary production of sex steroids in females, reverses these differences.

Objective: We hypothesized that sex differences in response to P chabaudi may be mediated by differential synthesis of IFN-gamma and IL-10 that is influenced by estrogen, progesterone, or both.

Immunological mechanisms mediating hantavirus persistence in rodent reservoirs.

Hantaviruses, similar to several emerging zoonotic viruses, persistently infect their natural reservoir hosts, without causing overt signs of disease. Spillover to incidental human hosts results in morbidity and mortality mediated by excessive proinflammatory and cellular immune responses. The mechanisms mediating the persistence of hantaviruses and the absence of clinical symptoms in rodent reservoirs are only starting to be uncovered.

Corticosteroids modulate Seoul virus infection, regulatory T-cell responses and matrix metalloprotease 9 expression in male, but not female, Norway rats.

Human hantaviral disease is mediated by excessive proinflammatory and CD8+ T-cell responses, which can be alleviated by administration of corticosteroids. In contrast with humans, male rats that are infected with their species-specific hantavirus, Seoul virus (SEOV), have reduced proinflammatory and elevated regulatory T-cell responses in tissues where virus persists. To determine the effects of glucocorticoids on SEOV persistence and immune responses during infection, male and female Norway rats received sham surgeries (sham) or were adrenalectomized (ADX0), in some of which corticosterone was replaced at low (ADX10) or high (ADX80) doses.

Seoul virus enhances regulatory and reduces proinflammatory responses in male Norway rats.

Zoonotic pathogens, including hantaviruses, are maintained in the environment by causing persistent infection in the absence of disease in their reservoir hosts. Spillover of hantaviruses to humans can cause severe disease that is mediated by excessive proinflammatory responses. The mechanisms mediating hantaviral persistence in rodent reservoirs remain largely unknown.

A survey of rodent-borne pathogens carried by wild-caught Norway rats: a potential threat to laboratory rodent colonies.

Unintentional infection of laboratory rodents can compromise scientific research as well as the health of the animals and animal handlers. The source of contamination often is unknown, but may be introduced by wild rats from surrounding environments. To determine whether rats in Baltimore, Maryland, USA carry infectious agents commonly found in laboratory rodent colonies, we live-trapped 162 rats during 2005 to 2006 and screened them for a panel of viruses, bacteria and parasites.

Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host.

Hantaviruses are zoonotic pathogens that maintain a persistent infection in their reservoir hosts, yet the mechanisms mediating persistence remain unknown. Regulatory T cell responses cause persistent infection by suppressing proinflammatory and effector T cell activity; hantaviruses may exploit these responses to cause persistence. To test this hypothesis, male Norway rats were inoculated with Seoul virus and regulatory T cells were monitored during infection.

Elevated testosterone and reduced 5-HIAA concentrations are associated with wounding and hantavirus infection in male Norway rats.

Among rodents that carry hantaviruses, males are more likely to engage in aggression and to be infected than females. One mode of hantavirus transmission is via the passage of virus in saliva during wounding. The extent to which hantaviruses cause physiological changes in their rodent host that increase aggression and, therefore, virus transmission has not been fully documented.

Serologic evidence for Rickettsia typhi and an ehrlichial agent in Norway rats from Baltimore, Maryland, USA.

We screened serum from 90 Norway rats trapped in East Baltimore, Maryland, USA, from April to November 2005 for antibodies against Rickettsia typhi and Ehrlichia chaffeensis. Six rats had positive titers of > or = 1:64 against R. typhi and did not react with R.

Norway rat population in Baltimore, Maryland, 2004.

Norway rats are reservoirs for several zoonotic agents, including hantaviruses, and are implicated in the transmission of pathogens to humans in urban environments. The rat population of Baltimore, Maryland was estimated from surveys in 1949 and again in 1952, but has not been evaluated for more than 50 years. Previously identified sociodemographic risk factors for rat infestation, including median income, human density, and percentage of rental properties, were used to categorize census block groups in Baltimore.