Human Metapneumovirus (HMPV) Genetics: The Genes and Genomic Composition
Introduction
Human
Metapneumovirus (hMPV) is a negative sense-single-stranded non segmented RNA virus. It is
classified in the family Pneumoviridae under the Mononegavirales order of
viruses. It was discovered in 2001 and identified as a respiratory tract-infecting
virus. It can infect individuals of all age groups but infants, young children,
old persons, and immunocompromised individuals are easy targets. It has gained
attention all over the world due to its recent outbreak in China. New cases of hMPV
infection are continuously reported in other parts of the world also including
India a densely populated country.
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| Diagrammatic Genomic Structure of Human Metapneumovirus (hMPV) |
Gene and Genomic Composition
The
genome of Human Metapneumovirus (hMPV) consists of a single-stranded,
negative-sense non-segmented RNA molecule. Its genome consists of approximately
13,200 nucleotides having eight regions each specific for one gene. These genes
are named N-gene, P-gene, M-gene, F-gene, M2-gene, SH-gene, G-gene and L-gene arranged
in the order: 3'-N-P-M-F-M2(-1 and -2)-SH-G-L-5’ on RNA strand and encode for
at least nine proteins. All genes code for one protein except the M2- gene
which codes for two proteins. The details of genome regions and proteins coded
by them are as follows:
N- Gene
N-
gene encodes for nucleoprotein (N protein) which is involved in the formation
of nucleocapsid. This protein binds with the negative-sense-single-stranded RNA
and is responsible for its encapsidation and protection of it.
P- Gene
P-
gene encodes for phosphoprotein (P protein) which is involved in viral
replication and transcription. The phosphoprotein acts as a co-factor of the viral
polymerase enzyme protein (L protein). This complex is required for
stabilization and the synthesis of new genetic material upon interaction with
the RNA-N protein complex.
M- Gene
The
M-gene encodes for Matrix protein (M protein) which is the major component of
the virus and involved in the assembling and budding of the virus. This protein
consists of the high-affinity binding site for Ca+ ions. Interestingly
it is secreted by infected cells in soluble form. It is also reported that it
can induce the secretion of inflammatory cytokines in in vitro cultures.
F- Gene
F-
region codes for Fusion glycoprotein (F protein) which is embedded on the outer
surface of the virus envelope in the form of spikes. It facilitates the fusion
of the virus with the membrane of host cells. This protein is considered the
most conserved protein among all proteins associated with hMPV.
M2- Gene
The
M2 gene consists of two portions M2-1 and M2-2 which encodes for two proteins
i.e. Putative transcription factor (M2-1 protein) and Putative transcription
factor (M2-1 protein). It is essential to mention that the gene encoding the M2
proteins contains two open reading frames (ORF) that lead to the expression of
either the M2-1 or M2-2 protein. The M2-1/2 proteins play a role in modulating
the processivity of the RNA polymerase involved in the regulation of transcription
of RNA. The M2-1/2 proteins are also responsible for the modulation of the
immune response produced by the host cells.
An epitope from the M2-1 protein stimulates a protective CTL (Cytotoxic
T lymphocyte) response. CTL responses
are the protective action by host cells to control viral infection. M2- 2
inhibits the TLR (Toll-like receptors) driven responses of host cells and is considered
one of the main molecular sensors targeted by hMPV to avoid its detection by
host immune cells.
SH- Gene
SH
gene encodes for small hydrophobic glycoprotein (SH protein) the function of
this is not understood completely. It might play a role in virus-host
interaction. The small hydrophobic protein may play different roles in the
modulation of the innate immune response (such as the inhibition of the
interferon (IFN) response) by inhibiting their synthesis pathways. It may also
have a function as a viroporin that alters the membrane permeability and blocks
the signalling of interferons which in turn suppresses the immune response of
the body toward viral infection.
G- Gene
G-gene
encodes for attachment glycoprotein (G protein) present on the outer surface of
envelopes in the form of spikes. It helps in the attachment of the virus with
the host cell by binding to cellular glycosaminoglycans which facilitate the
attachment of the viral particles to the cells of the host cell to initiate
infection. There is evidence that indicates the G protein contribution to the
inhibition of the IFN-I response of the host. It may also contribute to the recruitment of
neutrophils in the airways of the respiratory path.
L- Gene
L-gene
encodes for Viral polymerase enzyme protein (L protein) that facilitates
replication and transcription in the hMPV virus. It is a large polymerase
protein that has binding sites for zinc and exhibits multifunctional catalytic
activity. It is the one protein that is responsible for the synthesis of new
genetic material, along with the cofactors M2-1 and M2-2 proteins.
HMPV Variants
Human
Metapneumovirus (hMPV) has been classified into two main groups, i.e., A and B,
and further subdivided into A1, A2, B1, and B2, based on genetic analysis.
According
to Barbara Huck et al. 2006, the analysis of the whole genome of hMPV
showed that the virus exists in two genotypes A and B. These two genotypes are
further divided into subgroups A1, A2, B1, and B2 depending upon the
variability of a sequence of (G) and (F) glycoproteins. The subgroup A2 is
further subdivided into A2a and A2b.
Recently,
Zhibo Xie et al.
2021 reported unique hMPV
variants having duplication in the G- gene with 180 nt duplications (nt-dup) in
the G gene and a 111 nt-dup.
Conclusion
The
phosphoprotein (P), nucleocapsid protein (N), and viral polymerase protein (L)
are essential proteins for viral RNA synthesis. M2-1 protein appears to be
necessary for hMPV replication in vivo. The
study of the genomic structure of hMPV by several groups around the globe has
yielded substantial information regarding genes and proteins encoded by them.
This enhances our understanding to control the infection caused by Human
Metapneumovirus hMPV. However, there are still many gaps of knowledge regarding
the regulation of the antiviral response to hMPV that need to be defined such
as the role of other less-known subtypes of IFN in hMPV infection. The
phosphoprotein (P), nucleocapsid protein (N), and viral polymerase protein (L)
are essential proteins for viral RNA synthesis. M2-1 protein appears to be
necessary for hMPV replication in vivo. The
study of the genomic structure of hMPV by several groups around the globe has
yielded substantial information regarding genes and proteins encoded by them.
This enhances our understanding to control the infection caused by Human
Metapneumovirus hMPV. However, there are still many gaps of knowledge regarding
the regulation of the antiviral response to hMPV that need to be defined such
as the role of other less-known subtypes of IFN in hMPV infection.
Frequently Asked Questions(FAQ): Human Metapneumovirus Genetics
Is Human Metapneumovirus (HMPV) a DNA or RNA virus?
Human Metapneumovirus (hMPV) is not a DNA virus. It is an RNA virus. It consists of negative sense single-stranded RNA molecules as genetic material. The RNA molecule of hMPV consists of eight gene templates.
What are the genotypes of Human Metapneumovirus (hMPV).
Human Metapneumovirus (hMPV) has two main genotypes A and B. Each genotype is further divided into two subtypes A1, A2 and B1, B2 based on variation in gene sequences. The subtype B2 is further subdivided into A2a and A2b.
How big is Human Metapneumovirus (hMPV) genome?
The genome of Human Metapneumovirus (hMPV) consists of RNA molecules of approximately 13200 nucleotides. It consists of eight genes arranged in 3'-N-P-M-F-M2(-1 and -2)-SH-G-L-5’ on RNA strand and encodes for nine proteins each coding one protein except the M2 gene which code for two proteins.
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