ABSTRACT
Sequences analysis of hMPV has shown a genomic organization, 3’-N-P-M-F-M2-SH-G-L-5’ that is similar to that
previously described for AMPV [2]. The hMPV is believed to express nine proteins. These proteins are grouped as either integral membrane proteins embedded in the virus envelope, or internal proteins, which associate with the virus nucleocapsid beneath the envelope.The N (nucleoprotein), P (phosphoprotein), and L (polymerase) are replication proteins in the nucleocapsid. The M2 gene is predicted to encode two proteins, M2-1 and M2-2. The M2-1 protein is a transcription factor that interacts with the RNP, and the M2-2 protein plays a role in virus genome replication. The M (matrix) protein surrounds the RNP beneath the envelope and is believed to coordinate viral assembly by interfacing viral nucleocapsids with the surface membrane protein. The F, G, and SH (small hydrophobic) are integral membrane proteins on the surface of infected cells and virion particles [6]. The F protein is classic Type I integral membrane protein that facilitate membrane fusion of cell membrane and virus envelope during the initial stages of virus entry. Schowalter et al. demonstrated that hMPV F protein-promoted cell-cell fusion is stimulated by exposure to low pH, in contrast to what is observed for other paramyxovirus F proteins. They hypothesized that hMPV uses the low pH of the endocytic pathway to enhance infectivity [7]. Using prototype F proteins representing the four hMPV genetic lineages, Herfst et al. detected low-pHdependent fusion only with some lineage A proteins and not with lineage B proteins. It was shown that a glycine at position 294 was responsible for the low-pH requirement in lineage A proteins. In addition, he showed only 6% of all hMPV lineage A F sequences have 294G, and none of the lineage B sequences have 294G. Thus, he concluded that the acidic pH is not a general trigger of hMPV F proteins for activity [3]. The G protein is the predicted attachment protein. It differs from RSV and AMPV G protein in that it lacks a cytosine noose structure. Bao et al. studied the role of hMPV G protein in cellular signaling and identied G protein as
43.1 Introduction .................................................................................................................................................................... 479 43.1.1 Taxonomy and Classication ............................................................................................................................ 479 43.1.2 Structural and Nonstructural Proteins .............................................................................................................. 479 43.1.3 Biology .............................................................................................................................................................. 480 43.1.4 Clinical Manifestation, Pathogenesis, and Epidemiology ................................................................................ 480 43.1.5 Laboratory Diagnosis ........................................................................................................................................ 481
43.2 Methods .......................................................................................................................................................................... 482 43.2.1 Sample Preparation ........................................................................................................................................... 482 43.2.2 Detection Procedures ........................................................................................................................................ 482
43.3 Conclusion ...................................................................................................................................................................... 484 References ................................................................................................................................................................................. 484
an important virulence factor. They demonstrated that the G protein inhibited the production of important immune and antiviral mediators by targeting RIG-I, a major intracellular viral RNA sensor [8]. Biacchesi et al. evaluated recombinant hMPV in which the SH, G, or M2 gene or open reading frame was deleted by reverse genetics for replication and vaccine efcacy following topical administration to the respiratory tract of African green monkeys. Replication of the delta SH virus was only marginally less efcient than that of wild-type hMPV, whereas the replication of delta G and delta M2-2 viruses were reduced six-fold and 160-fold in the upper respiratory tract and 3200-fold and 4000-fold in the lower respiratory tract, respectively. They concluded that none of these proteins were essential for hMPV replication in a primate host. These gene-deleted viruses were highly immunogenic and protective against wild-type hMPV challenge and promising vaccine candidates [2]. Herd et al. reported cytotoxic T lymphocyte (CTL) responses that may control hMPV infection in humans [13]. They evaluated major histocompatibility complex (MHC) class I T-cell immunity in seven patients with previous hMPV respiratory disease. CTL response was present in most patients and to most hMPV proteins. They provided the rst report of MHC class I T-cell mediated immunity to hMPV in humans.
