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\begin{document}

\title{Cat Que Virus (CQV): A potential threat of the tropics? ``One Health
Approach'' to avert catastrophe: a narrative review}



\author[1]{Balasubramanian Ganesh}%
\author[1]{Thangarasu Rajakumar}%
\author[2]{Sridharan Vasumathy}%
\author[2]{Sridharan Sowmya}%
\author[1]{Natesan Manikandan}%
\author[3]{Harpreet Kaur}%
\affil[1]{ICMR-National Institute of Epidemiology}%
\affil[2]{University of Madras - Guindy Campus}%
\affil[3]{Indian Council of Medical Research}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
The world is now experiencing the catastrophe of global pandemic
`COVID-19', most serious public health crises in this century. Recently,
another virus named ``Cat Que Virus'' (CQV) seems to be causing its
terrible repercussions in the worlds' largest populous country `China',
the origin of SARS-CoV during 2002-2003, and the current pandemic
SARS-CoV-2 since December 2019. Recently, the presence of IgG antibody
among two persons in the state of Karnataka for CQV was reported in
India, the worlds' second-largest populous country. This means the virus
is in circulation in the sub-continent. The presence of the vector
mosquitoes (Aedes species, Culex species) and the ambient climatic
conditions suitable for vector breeding in the country needs to be taken
into account while planning to implement holistic strategies appropriate
for control and preventive measures. ``One Health approach'' is the
topmost option covering humans, animals/vectors and the environment to
curb the spread/transmission of infectious diseases in general. It is
also necessary to study the transmission dynamics and pattern of this
emerging virus, its life cycle, the natural reservoir of the virus, the
intermediate host and the accidental host with respect South-East Asia,
so that necessary remedial action can be planned well before an
epidemic. At present, the outbreak of CQV is certainly a warning to the
general population around the world. Considering the global imminent
health threats posed by CQV, there is an urgent need for active
surveillance, monitoring, effective vaccination, and a standard
treatment modality of this disease. Given the epidemiological aspect of
CQV, control and prevention measures are essential to stop the spread of
the virus. At present, there is no information available on CQV;
however, this current review article has covered the required data,
which will be helpful to control the spread of the CQV.%
\end{abstract}%



\sloppy


\subsection*{Title of the manuscript:}

{\label{title-of-the-manuscript}}

Cat Que Virus (CQV): A potential threat of the tropics? ``One Health
Approach'' to avert catastrophe: a narrative review

\textbf{Running Title:}

Cat Que Virus - a narrative review

\textbf{Authors:}

Balasubramanian Ganesh\textsuperscript{1\#}, Thangarasu
Rajakumar\textsuperscript{1}, Sridharan Vasumathy\textsuperscript{2},
Sridharan Sowmya\textsuperscript{3}, Natesan
Manikandan\textsuperscript{1}, Harpreet Kaur\textsuperscript{2}

\textbf{Affiliation:}

\textsuperscript{1}ICMR-National Institute of Epidemiology (ICMR-NIE),
R-127, Second Main Road, TNHB, Ayapakkam, Chennai-600 077, Tamil Nadu,
India.

\textsuperscript{2}Centre for Advanced Studies in Botany,University of
Madras,Guindy,Chennai- 600 025, Tamil Nadu, India.

\textsuperscript{3}National Center for Nanoscience and
Nanotechnology,University of Madras,Guindy,Chennai- 600 025, Tamil Nadu,
India.

\textsuperscript{4}Indian Council of Medical Research (ICMR), V.
Ramalingaswami Bhawan, Ansari Nagar, New Delhi-110029, India.

\textsuperscript{\textbf{\#}}\textbf{Address of the Corresponding
author:}

Dr. B. Ganesh, M.Sc., Ph.D.,Scientist-D(Assistant Director),
Laboratory~Division, ICMR-National Institute of Epidemiology (ICMR-NIE),
Indian Council of Medical Research, Department of Health Research (DHR),
Ministry of Health \& Family Welfare, Government of India, R-127;
2\textsuperscript{nd}Main Road,~TNHB Layout,~Ayapakkam, Chennai-600 077,
Tamil Nadu, India.

Phone (Direct-line): +91-44-2613-6455; FAX: +91-44-2682-0464; Mobile:
+91-78109-43585

ORCID id:~https://orcid.org/0000-0002-1978-2650 Email:
niedrbganesh@gmail.com

\textbf{Email of the authors:}

Balasubramanian Ganesh (BG): niedrbganesh@gmail.com

Thangarasu Rajakumar (TR): rajkumar18388@gmail.com

Sridharan Vasumathy (SV):vasumathysridharan@gmail.com

Sridharan Sowmya (SS):sowmyasrithar@gmail.com

Natesan Manikandan (NM): maninatesan87@gmail.com

Harpreet Kaur (HK): kaurh.hq@icmr.gov.in

\textbf{Abstract:} (293 words)

The world is now experiencing the catastrophe of global pandemic
'COVID-19', most serious public health crises in this century. Recently,
another virus named ``Cat Que Virus'' (CQV) seems to be causing its
terrible repercussions in the worlds' largest populous country `China',
the origin of SARS-CoV during 2002-2003, and the current pandemic
SARS-CoV-2 since December 2019. Recently, the presence of IgG antibody
among two persons in the state of Karnataka for CQV was reported in
India, the worlds' second-largest populous country. This means the virus
is in circulation in the sub-continent. The presence of the vector
mosquitoes (Aedes species, Culex species) and the ambient climatic
conditions suitable for vector breeding in the country needs to be taken
into account while planning to implement holistic strategies appropriate
for control and preventive measures. ``One Health approach'' is the
topmost option covering humans, animals/vectors and the environment to
curb the spread/transmission of infectious diseases in general. It is
also necessary to study the transmission dynamics and pattern of this
emerging virus, its life cycle, the natural reservoir of the virus, the
intermediate host and the accidental host with respect South-East Asia,
so that necessary remedial action can be planned well before an
epidemic. At present, the outbreak of CQV is certainly a warning to the
general population around the world. Considering the global imminent
health threats posed by CQV, there is an urgent need for active
surveillance, monitoring, effective vaccination, and a standard
treatment modality of this disease. Given the epidemiological aspect of
CQV, control and prevention measures are essential to stop the spread of
the virus. At present, there is no information available on CQV;
however, this current review article has covered the required data,
which will be helpful to control the spread of the CQV.

\textbf{Keywords:} Cat Que Virus; \emph{Orthobunyaviruses} ;
Vector-borne infection; Tropical nations; Public health; Global threat;

\textbf{1. Introduction:} (1875 words)

The world is now facing one of the most destructive pandemics ever
recorded. Panic of death due to Corona Virus Disease-2019 (COVID-19) is
all around the world and under the influence of this outbreak, another
dangerous virus called Cat Que Virus (CQV) appears to have had its
dreadful consequences in China. CQV was first identified from the
mosquitoes of Cat Que Commune, Hoai Duc District of Ha Tay Province in
Northern Vietnam during the improved surveillance activities for
Japanese Encephalitis Virus (JEV), as well as surveys for arbovirus
activity in regions where Acute Encephalitis Syndrome (AES) cases had
occurred during the period of 2004 causing morbidity and mortality among
children due to acute febrile illness and non-JEV AES. Several people in
the world have been reported infected so far, and this outbreak is
gradually beginning to spread in India as well.The findings of the
recent study conducted by the ICMR-National Institute of Virology (NIV),
Punereported that 2 out of 883 human serum samples had anti-CQV IgG
antibodies. This indicates that these two individuals have been infected
by the virus at some point in time. In specific, CQV spreads through
pigs and species of mosquitoes known as\emph{Aedes}and\emph{Culex}
(\emph{Ae. aegypti, Cx. quinquefasciatus,} and \emph{Cx.
tritaeniorhynchus} ).Both of these life forms exist in India and are
vulnerable to CQV. CQV can cause diseases such as meningitis, acute
febrile illness, and pediatric encephalitis to humans (Shete et al.,
2020).

\textbf{2. Classification of CQV:}

The order \emph{Bunyavirales} is found to have more than 350 viruses
with tripartite, negative-sense, single-stranded RNA (ssRNA) genomes,
belonging to 9 viral families. The members of the \emph{Feraviridae,
Phenuiviridae, Fimoviridae, Nairoviridae, Peribunyaviridae,
Tospoviridae, Jonviridae} and \emph{Phasmaviridae} families are carried
and transmitted through arthropods, while the viruses of
the\emph{Hantaviridae} family are carried by rodents and are transmitted
through the communication of aerosolized excreta(Elliott, 2013; Whitmer
et al., 2018). \emph{Fimoviridae} and \emph{Tospoviridae} family viruses
infect plants, while the viruses of family \emph{Nairoviridae}
,\emph{Peribunyaviridae} , and \emph{Phenuiviridae} can transmit the
disease to vertebrates. Genus \emph{Orthobunyavirus} is the largest
genus in the \emph{Peribunyaviridae} family that contains more than 170
viruses. \emph{Orthobunyaviruses} are categorized into 49 species and 19
serogroup complexes (Briese et al., 2013; Maes et al., 2018),consisting
of extremely diverse arboviruses (Nguyen et al., 2013). Simbu serogroup
has been the largest of these with 25 viruses isolated till date (Ladner
et al., 2014) and with seven species complexes such as\emph{Akabane,
Simbu, Oropouche, Shuni, Sathuperi, Shamonda,} and\emph{Manzanilla}
(Zhang et al., 2015; Saeed et al., 2001). CQV is one of the members of
the\emph{Manzanilla} species complex belonging to the Simbu serogroup
(Figure 1).

\textbf{3. Symptoms and complicationsof CQV (Diseases in humans):}

In presenttimes, growing numbers of \emph{bunyaviruses} have been
recognized as the main human pathogens. Amongst the
170\emph{bunyaviruses} , 60 viruses can induce diseases to humans,
containingpediatric encephalitis(\emph{La Cross virus} ),fever and joint
pain (\emph{Oropouche virus} ), meningitis (\emph{Cache valley virus} ),
Jamestown canyon encephalitis (\emph{Jamestown canyon virus} ), febrile
illness (\emph{Guaroa virus} ), hemorrhagic fever (\emph{Garissa virus}
),influenza-like symptoms (\emph{Tahyna virus} ) and the recent research
were reported that CQV has caused diseases like acute febrile illness
(high fever), pediatric encephalitis (inflammation of the brain) and
meningitis (inflammation of the meninges)in human beings (Nguyen et al.,
2013; Bewick et al., 2016; Treangen et al., 2016; Pastula et al., 2015;
Aguilar et al., 2010; Shete et al., 2020).

\textbf{4. Epidemiology of CQV (Origin and Transmission):}

CQV was first isolated in 2004 from mosquitoes and reported during the
surveillance of arboviruses in acute pediatric encephalitis cases in
Vietnam (Bryant et al., 2005) and late in Uganda (Mossel et al., 2017).
Viruses of family \emph{Peribunyaviridae} infect the vertebrates and
reside in a zoonotic infection cycle that spreads across livestock and
human beings through an arthropod intermediate (Saeed et al., 2001).
Globally, arboviruses (arthropod-borne viruses) have turned
into a major public health concern with the emergence and re-emergence
of arboviral diseases. Most of the arboviruses act as a zoonotic
spillover from an infected reservoir hosts (dogs, mosquitoes, birds, and
ruminants) to humans (accidental host) (Go et al., 2014; Bodewes and
Kuiken, 2018), i.e.,the spread of a pathogen from an infected vertebrate
to a human is caused by mosquito bite (Figure-2) (Whitmer et al., 2018).

\textbf{5. Genome structure of CQV:}

Often, the total genome size of \emph{bunyaviruses} ranges from 11 to 19
kb and around 80-120 nm in diameter (Schmaljohn,
1996).\emph{Bunyaviruses} have tripartite genomes containing a large
(L), medium (M), and small (S) RNA segments. Among this, the L segment
encodesRNA-dependent RNA polymerase(RdRp), which is necessary for mRNA
synthesis and replication of the viral RNA. The M segment encodes viral
glycoproteins, which ison the viral surface and help the virus in
attaching and entering into the host cell. The S segment encodes the
nucleocapsidprotein. Both ends of each gene segmentareenclosed with 5'-
and 3'-UTRs of various lengths (Ariza et al., 2013; Zhang et al.,
2015).Most of the \emph{bunyaviruses}have a negative-sense L and M
segment. The S segment of the genus\emph{Phlebovirus} (Elliott and
Brennan, 2014) and both M and S segment of the genus \emph{Tospovirus}
(Lima et al., 2016) are ambisense. The ambisense M segment codes for
glycoprotein (Gc and Gn) in the negative sense and a nonstructural
protein (NSm) in the positive sense. The ambisense S segment codes for
the viral nucleoprotein (N) in the negative sense and a nonstructural
protein (NSs) in the positive sense(Figure 3) (Lima et al., 2016;
Bouloy, 1991).

\textbf{6. Pathobiology of CQV:}

The ambisense genome of \emph{bunyaviruses} including the CQV requires
two rounds of transcription to be completed. Viral entry into its host
cell occurs through the receptor-mediated endocytosis and the following
stepstake place in the cytoplasm. Cell receptors are not definedfor
several\emph{bunyaviruses} (Lozach et al., 2010; Santos et al., 2008;
Jin et al., 2002), but those that contribute to the binding
ofsome\emph{bunyaviruses} contain integrins and other cell receptor
proteins,e.g.,gC1qR/p32, which is expressed on dendritic cells,
platelets, endothelial cells and lymphocytes (Albornoz et al., 2016). As
the genome of single-stranded, negative-sense RNA viruses cannot be
directly translated, the first step after permeation of the host cell
and uncoating in the triggering of the virion RNA polymerase and its
transcription of viral mRNAs from each of the three virion
RNAs.Afterward primary viral mRNA transcription and translation,
replication of the virion RNA takes place and the second round of
transcription instigates, with favoredamplification of the genes that
encode structural proteins required for virion synthesis.
(https://www.sciencedirect.com/science/article/pii/B9780128009468000222).Virions
mature through budding using intracytoplasmic vesicles related to the
Golgi complex and are released by the transport of vesicles through the
cytoplasm and consequent exocytosis from the plasma membranes (Figure-4)
(Weber et al., 2002; https://en.wikipedia.org/wiki/Bunyavirales).

\textbf{7. Diagnosis:}

Most of the diagnostic methods of this virus are carried by the
identification of antigen in tissues (immunofluorescence) or
serologically by IgG and IgM antibody (ELISA) (Bastos et al., 2012). The
IgM capture ELISA method is carried out as a primary diagnostic tool,
but reverse transcription-polymerase chain reaction (RT-tests are now
accessible for identification of the CQV (Zhang et al., 2015; Ladner et
al., 2014). Accurate confirmation of the presence of
accuratevirus can only bedone through conventional RT-PCRthat is
followed by sequencing.However, an earlierstudy has been reported that
the CQVhas been isolated and then diagnosed by the next-generation
sequencing (NGS) method.NGS of agents causing idiopathic human
infections have been important in the detection of novel viruses(Whitmer
et al., 2018; Yadav et al., 2016). Recently, a precise anda very
sensitive multiplexed one-step RT-qPCR were assessed for CQV
identification inthe cell supernatants and mouse tissues (Naveca et al.,
2017).

\textbf{8. Prevention by ``One Health approach'':}

One Health (OH) approach has been described by the American Veterinary
Medical Association as an integrative effort of multiple disciplines
working locally, nationally and globally to gain optimal health for the
humans, animals and the environment (American Veterinary Medical
Association, 2008). The OH would be useful for a better understanding of
the emerging and re-emerging diseases epidemiology, transmission
dynamics and pathobiology. Hypothetically, different countries have
approached implementing the principles of OH in various infectious
diseases with variable success and challenges (Okello et al., 2014).
Previously, the Rift Valley Fever (RVF) in Eastern Africa Region during
2006-07 outbreak played a vital role in galvanizing collaboration in OH
approaches among researchers, international organizations and government
departments to alleviate effects of future outbreaks and catalyzed the
essential for perfect understanding and implementation of OH approach
with an attention on supporting continued animal health surveillance
activities (Breiman et al., 2010). RVF caused by a virus, namely
phlebovirus that causesthe disease to animals and mosquitoes and can
spread both by animal secretions and mosquito (\emph{Aedes} ) bites
(Flick and Bouloy, 2005; Linthicum et al., 1998). China has been
implementing OH approaches for the coronavirus outbreaks in thepast and
the present viz. SARS in 2002-03 and SARS-CoV-2 since 2019 and also for
various other infectious diseases as well, which may have been prevented
unnoticed (Menachery et al., 2015; Wu et al., 2016; Tan et al., 2017;
Zheng et al., 2019; El Zowalaty and J\selectlanguage{ngerman}ärhult, 2020).Several studies
reported that implementing OH approach against COVD-19 (Yoo and Yoo,
2020; Bonilla-Aldana et al., 2020).India also implemented OH
surveillance system against COVD-19, which may be helpful tomitigate CQV
infection on the whole (Yasobant et al., 2020; Manoj, 2020) to avoid
huge loss.

\textbf{9. Treatment:}

As of now, there is nospecifictreatmentmethodfor the infection with CQV.
In severe cases, intensive medical care is essential, with the constant
monitoring of respiratory activity, control of fluid and electrolyte
balance, and the prevention of secondary infections. Ways to prevent the
CQV transmission and spread are similar to those routine preventive
measuresfor the spread of other infectious virusestransmittedby
mosquitoes (Carpenter et al., 2013; Sakkas et al., 2018).The use of
insect repellent, anti-mosquito lotions, wearing a cloth that covers the
arms and legs, and proper closingof window screens can reduce exposure
to mosquito bites, thereby reduging the virus transmission.As an
alternative, several natural compounds (picaridin, pyrethrins, and
azadirachtin) and plant-derived essential oils (levanter, neem,
geraniol, and eucalyptus) have been recommended as mosquito repellents
(Carpenter et al., 2013; Hoch et al., 1986). Additionally, source
reduction, i.e., removal of stagnant open water sources, including water
in flower vases, potted plants, man-made containers, water-circualted
air-coolers, referigeratorsdeforst water collection containers, etc.,
where mosquitoes tend to breed both indoor and outdoors around our house
premises, and terrace.Most importantly, followgeneral hygiene, limiting
contact with vector saliva, urine, feces, or bedding might prevent the
spread of the virus (González et al., 2016).

\textbf{10. Conclusion and Future perspectives:}

CQV is zoonotic and originates from pigs and/or mosquitoes. In Vietnam,
CQV was first isolated in 2004 and was later discovered in China.
Currently, the CQV is impacting and evolving in India and without the
proper precautionary measures, it might spread throughout the world. And
without proper awareness of this CQV outbreak, we may again be facing a
public health crisis or even a pandemic like situation as caused by
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Therefore,
to avoid a potential catastrophes in the near future, it is advisable to
follow universal preventive measures and precautionary mechanisms. At
present, without adequate medicine and vaccination, this is the only way
to reduce the incidence of such diseases. In the future, to monitor a
potential virus-related epidemic, we must have mandatory criteria for an
effective vaccine, treatment modality and medicine. Regarding CQV in
particular, there are several aspects that need a OH approach in order
to better understand the outbreak and to mitigate further epidemics of a
similar public health crisis in the future.

\textbf{Author Contributions: BG} conceptualized the work; \textbf{BG,
TR} and\textbf{NM} performed the literature search and \textbf{BG} wrote
the first draft of the manuscript.\textbf{SV} and\textbf{SS} gave
significant inputs and revised the manuscript.\textbf{BG,TR, SV,
SS}and\textbf{NM} performed the editing of the manuscript and revisions
by all the authors. The decision of the final version to be published
was agreed upon by all the authors.

\textbf{Funding:} The author(s) received no external funding for the
research,authorship, and/or publication of this article.

\textbf{Acknowledgments:} The Institutional Publication Committee (IPC)
of ICMR-National Institute of Epidemiology, Chennai for approval of the
study for publication.

\textbf{Conflicts of Interest:} The author(s) declared no potential
conflicts of interest with respect to the research, authorship, and/or
publication of this article.

\textbf{ORCID iD}

Dr. B. Ganesh, https://orcid.org/0000-0002-1978-2650

Dr. T. Rajakumar, https://orcid.org/0000-0003-1168-8464

Dr. N. Manikandan, https://orcid.org/0000-0002-3245-407X

\textbf{Figure Legends:}

\textbf{Figure-1:} Schematic representation of the Classification of Cat
Que Virus (CQV).

\textbf{Figure-2:} Schematic representation of genome of Cat Que Virus
(CQV). The genome comprises of Open Reading Frame (ORF) that encoding
nucleocapsid proteins (N), external glycoproteins (Gn and Gc), large
protein (L), medium protein (M), small protein (S), non-structural
proteins (NSs and NSm) and both ends of each gene segment contained
5'-untranslated region (5'-UTR) and 3'-untranslated region (3'-UTR) of
different lengths.

\textbf{Figure-3:} Schematic representation of life cycle and
transmission of Cat Que Virus (CQV). Birds and/or swine are the primary
reservoir hosts of CQV. The virus is transmitted to humans by the
infected mosquitoes that have fed from reservoir hosts.

\textbf{Figure-4:} Schematic representation of replication of Cat Que
Virus (CQV).

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