Comparative Analysis of Monkeypox Virus Infection of Cynomolgus Macaques by the Intravenous or Intrabronchial Inoculation Route
Reed F. JohnsonJulie DyallDan R. RaglandLouis HuzellaRussell ByrumCatherine JettMarisa St. ClaireAlvin L. SmithJason ParagasJoseph E. BlaneyPeter B. Jahrling
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Abstract:
Monkeypox virus (MPXV) infection has recently expanded in geographic distribution and can be fatal in up to 10% of cases. The intravenous (i.v.) inoculation of nonhuman primates (NHPs) results in an accelerated fulminant disease course compared to that of naturally occurring MPXV infection in humans. Alternative routes of inoculation are being investigated to define an NHP model of infection that more closely resembles natural disease progression. Our goal was to determine if the intrabronchial (i.b.) exposure of NHPs to MPXV results in a systemic disease that better resembles the progression of human MPXV infection. Here, we compared the disease course following an i.v. or i.b. inoculation of NHPs with 10-fold serial doses of MPXV Zaire. Classical pox-like disease was observed in NHPs administered a high virus dose by either route. Several key events were delayed in the highest doses tested of the i.b. model compared to the timing of the i.v. model, including the onset of fever, lesion appearance, peak viremia, viral shedding in nasal and oral swabs, peak cytokine levels, and time to reach endpoint criteria. Virus distribution across 19 tissues was largely unaffected by the inoculation route at the highest doses tested. The NHPs inoculated by the i.b. route developed a viral pneumonia that likely exacerbated disease progression. Based on the observations of the delayed onset of clinical and virological parameters and endpoint criteria that may more closely resemble those of human MPXV infection, the i.b. MPXV model should be considered for the further investigation of viral pathogenesis and countermeasures.Keywords:
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Monkeypox
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Viral Pneumonia
Although classical swine fever occurred in September 2018 for the first time in 26 years, its virulence is thought to be moderate based on field observations by veterinary authorities and our previous experimental infections. We quantified viremia and viral shedding in pigs infected with recent Japanese classical swine fever virus isolates, as well as a highly virulent strain. The results show that pigs infected with the Japanese strains exhibited lower viremia and viral shedding than those infected with the highly virulent strain. However, horizontal transmission occurred in pigs infected with the Japanese strains, similar to those infected with the highly virulent strain. Additionally, viremia and neuralization antibodies coexisted in pigs infected with the Japanese strains, presenting challenges for control measures.
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A large number of monkeypox (MPOX) cases have been reported in Europe and North America in 2022, and a new outbreak of this disease was declared. We describe a case of a patient with probable monkeypox during the height of this epidemic in Poland. The patient’s symptoms resolved within two weeks, but over the next two months, he developed community-acquired pneumonia requiring hospitalization and, subsequently, non-specific pleuritis. The simultaneous occurrence of such severe infections in a previously healthy young man is not typical and suggests a potential underlying cause. We believe the potential association of these diseases with probable monkeypox virus infection is very likely. Cases of monkeypox pneumonia, both viral and secondary bacterial, have already been reported in the literature. Cases of viral pleuritis in the course of MPOX in animals have also been described; however, to our knowledge, no similar cases have been described in humans to date. Our case indicates that it is important to monitor patients after MPOX in order to respond promptly to potentially life-threatening but, as of yet, not fully understood complications.
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The predictors for fatal adenovirus (AdV) pneumonia among immunocompetent adults are unclear. Laboratory-confirmed, hospitalized AdV pneumonia adults were prospectively enrolled in Beijing Chao-Yang hospital from March to June 2013. Clinical data and serial whole blood and respiratory tract secretions from such patients were collected. Quantitative real-time polymerase chain reaction was performed to quantify the viral load. A total of 14 AdV pneumonia cases were consecutively enrolled, and four of them were fatal. Ten cases were caused by AdV-55, three by AdV-7 and one by AdV-3. There were no differences in age, gender or underlying diseases between the patients in the fatal cases and surviving cases. At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log10 copies/ml, p = 0.023). All patients in fatal cases presented with viremia on day 12–14 (100% vs 66.7%, p = 0.017). A higher initial viral load in the respiratory tract and sustained viremia (more than 2 weeks) may be predictors for fatal clinical outcomes.
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【Objective】 To understand the dynamics of viremia,virus shedding and antibody responses in chickens inoculated with avian leukosis vrius subgroup J(ALV-J) and provide essential epidemiological data for prevention and eradicationo of ALV-J infection.【Method】 Viremia,virus shedding and antibody response were successively measured after inoculation with ALV-J strain HN0001 intraperitoneally,orally or in contact in SPF chickens at 1 day and 49 days.【Result】 The dynamics of viremia and antiboty responses were very different in chickens inoculated with ALV-J at different ages.Viremia and p27 in cloaca swabs started to be detected from the 2nd week after inoculation with ALV-J at 1-day-old.In the group inoculated intraperitoneally with ALV-J,71%(5/7) continuously demonstrated viremia and p27-shedding.Viremia and virus shedding lasted for at least 45 weeks in 3 chickens.Among them,only 1 chicken showed transient antibody reaction at 16-week-old,another 2 were in tolerant viremia without any antibody reactions.In the group inoculated orally with ALV-J,11%(1/9) demonstrated persistant viremia and p27-shedding but no antibody response,44%(4/9) showed transient viremia or p27-shedding,and then antibody responses from 8-week-old.No control bird kept in contact with inoculated birds in the same isolators demonstrated viremia or p27-shedding,and also no antibody responses.It indicated there was no horizontal infection.In chickens intraperitoneally inoculated with ALV-J at 49-day-old,neither viremia nor p27-shedding were detected in 5 separate testing during the 19th week after inoculation,but antibody reaction started to be detected 1 week after inoculation.In the orally inoculated chickens or the contacted control chicken,all samples were negative in vriremia,p27-shedding and antibody reactions.【Conclusion】 Inoculation with ALV-J at 1-day-old easily induced immune tolerence,chickens inoculated demonstrated persistant viremia or p27-shedding,but no antibody reactions.Chickens inoculated with ALV-J at 49-day-old,antibody could detected 1 week after inoculation,but no viremia and p27-shedding were detected.Inoculation routes significantly influenced the dynamic variety of ALV-J inoculation,intraperitoneally injection induced higher viremia levels and increased percentages with tolerant viremia when compared to oral inoculation.
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Equid herpesvirus-1 (EHV-1) outbreaks continue despite widely used vaccination. We demonstrated previously that an ORF1/ORF71 gene deletion mutant of the EHV-1 strain Ab4 (Ab4ΔORF1/71) is less virulent than its parent Ab4 virus. Here, we describe the Ab4 challenge infection evaluating protection induced by the Ab4ΔORF1/71 vaccine candidate. Susceptible control horses developed respiratory disease, fever, nasal shedding, and viremia. Full protection after challenge infection was observed in 5/5 previously Ab4 infected horses and 3/5 Ab4ΔORF1/71 horses. Two Ab4ΔORF1/71 horses developed short-lasting viremia and/or virus shedding. Protective immunity in the respiratory tract was characterized by pre-existing EHV-1-specific IgG4/7 antibodies, the absence of IFN-α secretion and rapidly increasing IgG4/7 upon challenge infection. Pre-existing systemic EHV-1-specific IgG4/7 highly correlated with protection. T-cell immunity was overall low. In conclusion, protective immunity against EHV-1 infection including prevention of viremia was associated with robust systemic and intranasal IgG4/7 antibodies suggesting immediate virus neutralization at the local site.
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Pandemic (H1N1) 2009 virus causes severe illness, including pneumonia, which leads to hospitalization and even death. To characterize the kinetic changes in viral load and identify factors of influence, we analyzed variables that could potentially influence the viral shedding time in a hospital-based cohort of 1,052 patients. Viral load was inversely correlated with number of days after the onset of fever and was maintained at a high level over the first 3 days. Patients with pneumonia had higher viral loads than those with bronchitis or upper respiratory tract infection. Median viral shedding time after the onset of symptoms was 9 days. Patients <13 years of age had a longer median viral shedding time than those >or=13 years of age (11 days vs. 7 days). These results suggest that younger children may require a longer isolation period and that patients with pneumonia may require treatment that is more aggressive than standard therapy for pandemic (H1N1) 2009 virus.
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Abstract Objective —To determine rapidity of spread and onset and duration of viremia, virus shedding, and antibody production in parrots naturally infected with avian polyomavirus (APV). Design —Case series. Animals —92 parrots in 2 aviaries. Procedure —Blood samples were obtained from parrots naturally exposed to APV during a 3- to 4-month period for determination of serum virus neutralizing antibody and detection of viral DNA. Nestlings from the next year's hatch were monitored for APV infection. Results —The first indication of inapparent infection was viremia, which developed simultaneously with or was followed within 1 week by cloacal virus shedding and antibody production. Cloacal virus shedding continued after viremia ceased. During viremia, viral DNA was detected continuously in blood samples. Viral DNA was detected in serial cloacal swab specimens in most birds, but it was detected inconsistently in 6 birds and not detected in 3 birds, even though these birds were viremic. Duration of cloacal virus shedding was ≤ 4.5 months. In 1 aviary, prevalence of infection was 88% and dissemination of virus through the 3-room building required 4.5 months. In the second aviary, a single-room nursery, prevalence of infection was ≥ 90%. For all affected birds, infection could be detected 18 days after the first death. Conclusion and Clinical Relevance —If a single sampling is used for polymerase chain reaction detection of viral DNA, blood and cloacal swab specimens are required. In nestling nonbudgerigar parrots, cloacal virus shedding may persist for 4.5 months. Management protocols alone are sufficient to prevent introduction of APV into a nursery. ( J Am Vet Med Assoc 2000;217:32–36)
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ABSTRACT COVID-19 has surfaced as a multi-organ disease predominantly affecting the respiratory system. Detection of the viral RNA through reverse transcriptase–PCR (RT-PCR) from a nasopharyngeal or throat sample is the preferred method of diagnosis. Recent evidence has suggested that COVID-19 patients can shed the SARS-CoV-2 for several weeks. Herein, we report six cases of COVID-19 who had persistently positive SARS-CoV-2 on repeat RT-PCR testing reaching up to 9 weeks. The spectrum of cases described ranges from asymptomatic infection to severe COVID-19 pneumonia. A full understanding of the virus’s transmission dynamics needs further research. Prolonged viral shedding currently has unclear implications on the management and isolation decisions—the role of the cycle threshold (Ct) value in guiding therapeutic decisions is yet to be clarified. More data on the relationship between Ct values and viral cultivation are needed, especially in patients with prolonged viral shedding, to understand the virus’s viability and infectivity.
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