section_path: Life cycle and reproduction
section_name: Life cycle and reproduction
paragraph_text: Life cycle and reproduction
  
  hMPV is estimated to have a 3–6 day incubation period and is often most active during the later winter and spring seasons in temperate climates, overlapping with the RSV and influenza seasons and possibly allowing for repeated infection. As of 2012, hMPV and its replication cycle were not well understood. Some of the principal steps of hMPV's replication cycle were studied with experiments based on the viral life cycles and reproductive measures of the rest of the Paramyxoviridae family.
  
  The first step of the hMPV replication cycle is attachment to the host cell, specifically the epithelial cells of the respiratory tract, using the G protein. This G protein contains a hydrophobic region that acts as an uncleaved signal peptide and a membrane anchor to facilitate its binding; however, because recombinant viruses that lack the G protein have still been able to replicate in vitro and in vivo, it seems that attachment via the G protein is not required for rest of the replication cycle.
  
  Next in the cycle is the fusion of the viral and host membranes which is likely mediated by the F protein. Though the fusion mechanism is very similar to that of other Paramyxoviridae family members and involves conformational changes of the F protein, the mechanism for hMPV does not depend on the G protein for fusion like its family members, showing consistency with the previously mentioned idea that the G protein is not necessary for subsequent steps of the hMPV replication cycle. The fusion function of the F protein has been proven by its ability to bind to host cells via integrin αvβ1 using an Arginine-Glycine-Aspartate (RGD) motif, which is speculated to be the trigger for membrane fusion events.
  
  One main difference between hMPV and other Paramyxoviridae viruses' fusion mechanisms though is that hMPV's fusion events occur at acidic pH levels while other viruses' fusion events occur at neutral pH levels; however, more research needs to be conducted in this area to get a better understanding of what is different about the hMPV fusion mechanism and why. Although its specific function is uncertain, the presence of the SH glycoprotein does not appear to have any effects on replication kinetics, cytopathic effects, or plaque formation of hMPV.
  
  After fusion, the viral ribonucleoprotein (RNP) containing negative-sense viral RNA (vRNA) genome is released into the cytoplasm and acts as a template for mRNA and antigenomic cRNA synthesis. From here, most of our knowledge about hMPV transcription is derived from what we already know about RSV and other Paramyxoviridae viruses, including that leader and trailer sequences in the genome are partially complementary and act as promoters for transcription. We see that proteins N, P, and L dissociate from the vRNA and bind to each other to form the polymerase complex so that the genomic RNA can act as a matrix for viral transcription and replication in the cytoplasm.
  
  The final step in the replication process of hMPV that is relatively certain is the journeying of the envelope glycoproteins (F, G, and SH) to zones of membranous accumulation via the Golgi apparatus to be exposed at the surface of infected cells. This allows infected cells to merge with adjacent cells through the action of viral fusion proteins on the surface, effectively spreading the virus's genome. The rest of the replication cycle following RNA and viral protein synthesis are unclear and require further research.
  
  hMPV is estimated to have a 3–6 day incubation period and is often most active during the later winter and spring seasons in temperate climates, overlapping with the RSV and influenza seasons and possibly allowing for repeated infection. As of 2012, hMPV and its replication cycle were not well understood. Some of the principal steps of hMPV's replication cycle were studied with experiments based on the viral life cycles and reproductive measures of the rest of the Paramyxoviridae family.
  
  The first step of the hMPV replication cycle is attachment to the host cell, specifically the epithelial cells of the respiratory tract, using the G protein. This G protein contains a hydrophobic region that acts as an uncleaved signal peptide and a membrane anchor to facilitate its binding; however, because recombinant viruses that lack the G protein have still been able to replicate in vitro and in vivo, it seems that attachment via the G protein is not required for rest of the replication cycle.
  
  Next in the cycle is the fusion of the viral and host membranes which is likely mediated by the F protein. Though the fusion mechanism is very similar to that of other Paramyxoviridae family members and involves conformational changes of the F protein, the mechanism for hMPV does not depend on the G protein for fusion like its family members, showing consistency with the previously mentioned idea that the G protein is not necessary for subsequent steps of the hMPV replication cycle. The fusion function of the F protein has been proven by its ability to bind to host cells via integrin αvβ1 using an Arginine-Glycine-Aspartate (RGD) motif, which is speculated to be the trigger for membrane fusion events.
  
  One main difference between hMPV and other Paramyxoviridae viruses' fusion mechanisms though is that hMPV's fusion events occur at acidic pH levels while other viruses' fusion events occur at neutral pH levels; however, more research needs to be conducted in this area to get a better understanding of what is different about the hMPV fusion mechanism and why. Although its specific function is uncertain, the presence of the SH glycoprotein does not appear to have any effects on replication kinetics, cytopathic effects, or plaque formation of hMPV.
  
  After fusion, the viral ribonucleoprotein (RNP) containing negative-sense viral RNA (vRNA) genome is released into the cytoplasm and acts as a template for mRNA and antigenomic cRNA synthesis. From here, most of our knowledge about hMPV transcription is derived from what we already know about RSV and other Paramyxoviridae viruses, including that leader and trailer sequences in the genome are partially complementary and act as promoters for transcription. We see that proteins N, P, and L dissociate from the vRNA and bind to each other to form the polymerase complex so that the genomic RNA can act as a matrix for viral transcription and replication in the cytoplasm.
  
  The final step in the replication process of hMPV that is relatively certain is the journeying of the envelope glycoproteins (F, G, and SH) to zones of membranous accumulation via the Golgi apparatus to be exposed at the surface of infected cells. This allows infected cells to merge with adjacent cells through the action of viral fusion proteins on the surface, effectively spreading the virus's genome. The rest of the replication cycle following RNA and viral protein synthesis are unclear and require further research.