Orosomucoid-like protein 3, rhinovirus and asthma

Table 1 Orosomucoid-like protein 3 roles in regulating human rhinovirus infection

Regulating molecules and processes	The roles in human rhinovirus infection	Ref.
ICAM1	ORMDL3 regulates ICAM1 expression for influencing HRV adhesion and entrance and viral load	[56,61,62]
ER stress	ORMDL3 regulates ER stress and the ER stress can induce PERK and IRE1 pathways that affect HRV infection	[61,63,65]
Ceramide and S1P	ORMDL3 regulates ceramide and S1P levels. S1P and ceramide are responsible for cell survival, proliferation, apoptosis, differentiation and cell-cycle arrest; they also affect ICAM1 expression	[55,61,71,72,77]
ER-Golgi interface	HRV can both fragment the Golgi apparatus and block secretion. ORMDL3 regulates ER-Golgi interface through ER stress and sphingolipid metabolism	[61,84,85]
Glycolysis	ORMDL3 regulates glycolysis. Glycolysis can determine the extent of replication of HRVs in cells	[61,91]

ICAM1: Intercellular adhesion molecule 1; ORMDL3: Orosomucoid-like protein 3; HRV: Human rhinovirus; ER: Endoplasmic reticulum; S1P: Sphingosine-1-phosphate.

Table 2 The models for studying interaction of host and environmental factors

The available models	Advantages	Disadvantages
Monolayer cell models	Simplistic model; Easy to culture within short times	Cells underneath the medium, no connection to other types of cells and no tight junctions; Non-optimal physiologic response; The growth kinetics of bacteria, fungal or virus on monolayer are known to be different from human body
Air liquid interface model	Polarized differentiated airway epithelium containing ciliated epithelial cells, basal cells and mucus producing cells, mimicking human epithelium; It can be co-cultured with pathogens; Respiratory virus is known to show similar replication kinetics as in human body
3D human lung spheroid model	3D multicellular spheroids are small, tightly bound cellular aggregates that tend to form when cells are maintained under non-adherent conditions; Other cell types such as fibroblasts can be incorporated and can be co-cultured with pathogens
Animal models	In vivo	Have ethical issues and many results cannot be replicated in human studies; High cost; Time consuming, not applicable to high-throughput studies

3D: Three-dimensional.