Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters.
BACKGROUND
Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B).


RESULTS
Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi.


CONCLUSIONS
Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.|Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States of America.
Laura
L
Baseler
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Dana P
DP
Scott
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Greg
G
Saturday
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Eva
E
Horne
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Rebecca
R
Rosenke
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Tina
T
Thomas
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Kimberly
K
Meade-White
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Elaine
E
Haddock
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Heinz
H
Feldmann
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Emmie
http://orcid.org/0000-0002-9763-7758
E
de Wit
D056809:Alveolar Epithelial Cells / Q000821:virology; D000818:Animals; D002490:Central Nervous System / Q000821:virology; D006224:Cricetinae; D045464:Henipavirus Infections / Q000821:virology*; D006801:Humans; D007830:Larynx / Q000821:virology; D008168:Lung / Q000166:cytology / Q000473:pathology / Q000821:virology; D016676:Macrophages, Alveolar / Q000821:virology; D008647:Mesocricetus; D045405:Nipah Virus / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification* / Q000502:physiology*; D012367:RNA, Viral / Q000302:isolation & purification; D020545:Respiratory Mucosa / Q000821:virology; D014132:Trachea / Q000821:virology; D014420:Turbinates / Q000821:virology; D014779:Virus Replication
D012367:RNA, Viral