The guinea pig as a transmission model for human influenza viruses - PubMed (original) (raw)
The guinea pig as a transmission model for human influenza viruses
Anice C Lowen et al. Proc Natl Acad Sci U S A. 2006.
Abstract
The severity of epidemic and pandemic influenza outbreaks is dictated in part by the efficiency with which the causative strain transmits between human hosts. The mechanisms underlying influenza virus spread are poorly understood, in part because of the lack of a convenient animal model to study this phenomenon. Indeed, despite extremely efficient transmission among humans and virulence in the mouse model, we have shown that even the 1918 pandemic influenza virus does not transmit between mice. We therefore evaluated the guinea pig as a model mammalian host for influenza virus. Using the recent human isolate A/Panama/2007/99 (Pan/99) (H3N2) virus, we found that guinea pigs were highly susceptible to infection with the unadapted virus (ID(50) = 5 plaque-forming units). Pan/99 virus grew to high titers in the upper respiratory tract and was shed in nasal washings of infected animals. Moreover, influenza virus was transmitted from infected guinea pigs to noninfected guinea pigs housed in the same cage, an adjacent cage, and a cage placed 91 cm away. Our results demonstrate that influenza virus can pass between guinea pigs by means of droplet spread and thereby establish the suitability of the guinea pig as a model host for influenza virus transmission studies.
Conflict of interest statement
Conflict of interest statement: No conflicts declared.
Figures
Fig. 1.
Characteristics of Pan/99 virus infection in guinea pigs. Fourteen guinea pigs were infected intranasally with 103 pfu of Pan/99 virus. The number of infected animals evaluated on each day varied as follows: day 1, n = 14; days 2 and 3, n = 12; days 4 and 5, n = 10; days 6 and 7, n = 8; days 8 and 9, n = 6; days 10–14, n = 4. At all time points, two mock-infected animals were assessed. (A) Viral titers in nasal washings and lung homogenates. At the indicated time points, nasal washings were collected from all guinea pigs, and two animals were killed and their lungs were removed. Infectious content of nasal wash samples and lung homogenates were then determined by plaque assay (limit of detection was 10 pfu/ml or 30 pfu/g). Nasal wash titers are expressed in pfu/ml, and lung titers are expressed in pfu/g of lung. (B) Change in body temperature over the course of infection. Temperatures were measured twice daily from 2 days before infection to 14 days p.i. The average preinfection temperature for each animal was subtracted from each p.i. temperature to obtain the change in body temperature for each guinea pig; the average change in temperature for all guinea pigs was plotted. (C) Change in body weight over the course of infection. Body weight was assessed daily and is expressed as the average percentage change in body weight for each animal.
Fig. 2.
Transmission of Pan/99 virus from intranasally infected guinea pigs to uninfected contacts. Three animals were inoculated with 102 pfu of Pan/99 virus. At 24 h p.i., each of these animals was placed in a cage (designated 1, 2, or 3) with one uninfected guinea pig. Nasal washes were performed at 48-h intervals, starting from 48 h p.i. for the inoculated animals (24 h p.c.).
Fig. 3.
Droplet transmission of Pan/99 virus among guinea pigs. Representative results from two independent experiments are shown. Inoculated guinea pigs were given 103 pfu of Pan/99 virus intranasally and kept distant from sentinel animals until 24 h p.i. Nasal washes were performed at 48-h intervals, starting from 48 h p.i. for the inoculated animals. Cage layouts are shown in A; open, wire-top cages were placed on a shelf as shown; animals in cages 1 and 2 were infected. Viral titers in nasal wash samples are plotted in B; each curve corresponds to a single animal. “x” and “o” are used to distinguish two guinea pigs housed in the same cage; thus, 1x and 1o were housed in cage 1.
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