Invest Clin 64(1): 68 - 80, 2023 https://doi.org/10.54817/IC.v64n1a06
Corresponding author: José Luis Zambrano. Laboratorio de Virología Celular, Centro de Microbiología y Biología
Celular (CMBC), Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Miranda, Venezuela. E-mail:
jlzr.lab@gmail.com.
Web-tools for the genomic analysis of the
2022 Monkeypox virus global outbreak.
Zoila C. Moros1, Carmen L. Loureiro2, Rossana C. Jaspe2, Yoneira Sulbarán2,
Mariangel Delgado3, Olga Carolina Aristimuño1, Christopher Franco1,
Domingo J. Garzaro2, Mariajosé Rodríguez2, Héctor R. Rangel2,
Ferdinando Liprandi4, Flor H. Pujol2 and José Luis Zambrano1
1Laboratorio de Virología Celular, Centro de Microbiología y Biología Celular (CMBC),
Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Miranda,
Venezuela.
2Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular
(CMBC), Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas,
Miranda, Venezuela.
3Unidad de Microscopía Electrónica y Confocal, Centro de Microbiología y Biología
Celular (CMBC), Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas,
Miranda, Venezuela.
4Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular (CMBC),
Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Miranda,
Venezuela.
Keywords: Monkeypox virus; outbreak; genome analysis; web tools; database.
Abstract. The resources and platforms available on the internet for collect-
ing and sharing information and performing genomic sequence analysis have
made it possible to follow closely the evolution the evolution of SARS-CoV-2.
However, the current monkeypox outbreak in the world brings us back to the
need to use these resources to appraise the extent of this outbreak. The ob-
jective of this work was an analysis of the information presented so far in the
genomic database GISAID EpiPox™, using various tools available on the web.
The results indicate that the monkeypox outbreak is referred as MPXV clade II
B.1 lineage and sub-lineages, isolated from male patients mainly from the Euro-
pean and American continents. In the current scenario, the access to genomic
sequences, epidemiological information, and tools available to the scientific
community is of great importance for global public health in order to follow the
evolution of pathogens.
Monkeypox virus global outbreak 69
Vol. 64(1): 68 - 80, 2023
Herramientas web para el análisis genómico del virus
de la viruela símica durante el brote mundial de 2022.
Invest Clin 2023; 64 (1): 68 – 80
Palabras clave: virus de la viruela símica; brote; análisis genómico; herramientas web;
bases de datos.
Resumen. Los recursos y plataformas disponibles en Internet para reco-
pilar, compartir información y realizar análisis de secuencias genómicas han
permitido seguir de cerca la evolución del SARS-CoV-2. El actual brote global
de viruela del mono en el mundo, requiere de nuevo utilizar estos recursos para
conocer el alcance de este brote. El objetivo de este trabajo fue un análisis de
la información presentada hasta el momento en la base de datos genómica
EpiPox™ de GISAID, utilizando diversas herramientas disponibles en la web.
Los resultados indican que el brote de la viruela del mono o símica está refe-
rido al linaje y sub-linajes B.1 del clado II de MPXV, aislado principalmente de
pacientes hombres de Europa y América. En el escenario actual, el acceso a
las secuencias genómicas, la información epidemiológica, y las herramientas
disponibles para la comunidad científica son de gran importancia para la salud
pública mundial con el fin de seguir la evolución de los patógenos.
Received: 17-09-2022 Accepted: 29-10-2022
INTRODUCTION
The first half of 2022 marks the rise
of the seventh peak of the SARS-CoV-2 pan-
demic worldwide due to the different sub-lin-
eages of Omicron VOC 1. Simultaneously, in
May 2022, outbreaks of the monkeypox virus
(MPXV) were confirmed outside the African
continent. The first cases detected were in
the United Kingdom, related to travelers re-
turning from Nigeria, an African country that
has historically reported monkeypox cases.
However, this outbreak has spread to other
countries in Europe, America, Asia, Australia,
and other African countries. To date, more
than 55,000 cases and 15 deaths have been
reported in 75 countries worldwide 1.
During the emergence of the first cas-
es of monkeypox outside Africa, the World
Health Organization (WHO) stated that the
outbreak was considered of low impact on
the general population in the affected coun-
tries. However, in June 2022, the WHO de-
clared that the outbreak of MPXV poses an
evolving public health threat, confirming five
deaths in Africa from this outbreak. There-
fore, in July 2022, even without reaching a
consensus of the WHO’s Emergency Com-
mittee charged with assessing the outbreak,
Tedros Adhanom Ghebreyesus, the General
Director of WHO, declared that monkeypox
constituted an international emergency as
the outbreak met their requirements and
stated that the health care should be taken
as seriously as that of COVID-19 1.
MPXV is a species of the genus Ortho-
poxvirus of the family Poxviridae 2, included in
this viral group Variola (VARV) and Vaccinia
viruses (VACV) 3. The MPXV genome con-
sists of linear double-stranded DNA (≈198
kb) and it is covalently linked in its ends re-
gion by palindromic hairpins and inverted
70 Moros et al.
Investigación Clínica 64(1): 2023
terminal repeats (ITRs), which are formed
by hairpin loops, tandem repeats, and some
open reading frames (ORFs). Few conserved
genes encoding virus-cell interaction proteins
(ABCNMK) are located in the left and right
terminal regions of the genome. In contrast,
the more conserved genes (FEOPIGLJHD)
with housekeeping functions are located in
the central region of the genome4. It is known
that of the 90 of the more conserved ORFs
are known to be essential for poxvirus repli-
cation and morphogenesis. In contrast, many
of the additional so-called non-essential and
less conserved ORFs play a role in the differ-
ences in poxvirus host tropism, immunomod-
ulation, and pathogenesis, and the part that
many of the ORFs play is still unknown 3.
MPXV causes monkeypox, a neglected
zoonotic disease 5, and has a wide range of
hosts, including non-human primates, a vari-
ety of rodents (squirrels, rats, jerboa, wood-
chuck prairie dogs), civets, giant anteaters,
antelopes, opossums and humans 6. The nat-
ural reservoir of the virus is still unknown.
Monkeypox is characterized by a lower case-
fatality ratio than smallpox 7. The incuba-
tion period of monkeypox is usually eight
days but can range from four to 14 days 8.
Among the symptoms that people infected
with MPXV develop are fever, chills, muscle,
head and back pain. The most notorious sign
is the development of papular skin lesions
and rash 3. Although most of the reported
cases of 2022 MPXV outbreak are related to
male patients who have sex with men, the
monkeypox disease is not sexually transmit-
ted but it can be spread mainly by close skin-
to-skin contact between sexual partners 9.
MPXV are grouped into two clades:
Clade I (former Congo Basin) and Clade II
(former West Africa) (Fig. 1). The Clade I,
considered more pathogenic and found pri-
marily in the Democratic Republic of the
Congo and surrounding counties, was re-
sponsible for the first documented human
case of MPXV in 1970. The clade hMPXV-1A
II has been assigned as clade IIa lineages:
A.1, (sub-lineage A.1.1), A.2 and, with the
current MPXV outbreak in 2022 a newly
classified emerging clade IIb and lineage B.1
and sub-lineages: B.1.1, B.1.2, B.1.3, B.1.4,
B.1.5, B.1.6, B.1.7, B.1.8 10–12. Lineage and
sub-lineage assignments are based on 46
single-nucleotide polymorphisms (SNPs) ob-
served in the 2022 MPXV outbreak’s strains
compared with the NCBI Monkeypox refer-
ence sequence NC_063383 13.
With the COVID-19 pandemic, we have
learned an important lesson about the need
for global surveillance of SARS-CoV-2 ge-
netic sequences, as well as the importance
of sharing metadata in public databases ac-
cessible to the scientific community. Thus,
genomic surveillance has been an essential
resource for monitoring and tracking the
evolution of mutations that have driven the
development of new and more pathogenic
variants. This early genomic detection has
Fig.1. Evolutionary features of monkeypox virus.
Representation of the evolution of the cla-
des, lineages and sub-lineages of MPXV. Ba-
sed on the Nextstrain website information.
Lineages and sub-lineage colour by NextS-
train code colour.
Monkeypox virus global outbreak 71
Vol. 64(1): 68 - 80, 2023
raised our knowledge for the establishment
of better treatments, the study of potential
new drugs with antiviral activity, and new
vaccines. Additionally, genomic surveillance
has improved our understanding of how the
virus can enhance its spread, as well as the
geographic and temporal origin and the way
of the global spread of new variants, and vi-
sualize the viral evolution in real-time 14.
Among the global initiatives and ef-
forts to publicly share SARS-CoV-2 pandem-
ic metadata is the GISAID platform 15. The
GISAID Initiative promotes a rapid sharing
of data on all influenza viruses and the coro-
navirus that causes COVID-19, and ensures
open access to data free of charge to the sci-
entific community. GISAID was born to allow
public access to the latest avian influenza ge-
netic sequences and as an alternative to the
public domain sharing model by enabling
data sharing between WHO Collaborating
Centers and National Influenza Centers by
creating the EpiFlu™ database. In 2020,
the EpiCoV™ database was created at mo-
ment this new database contains more than
11 million complete SARS-CoV-2 sequences,
making the EpiCoV™ database the principal
repository for pandemic COVID-19.
For the current global outbreak of
MPXV, the GISAID initiative created in 2022
a database called EpiPox™. The goal of this
work is to know what epidemiological and
genomic information can this database pro-
vide us on MPXV risk to global public health,
using different web-tools currently available
for this type of study.
MATERIALS AND METHODS
Data Source and curation
Data were extracted from the GISAID
EpiPox™ database 15. The cut date for avail-
able data was September 2, 2022. The data
included in this study corresponded to the
following inclusion criteria: sequences avail-
able from April 1 to September 2, 2022, and
MXPV complete sequences with high cover-
age (less than 1% of undefined bases).
Data analysis
A multi-FASTA file of 940 complete
MXPV sequences with high coverage in-
cluding two reference sequences (Clade
I: hMpxV/DRC/CDC-005/1978, Clade IIa:
MpxV/USA/un-WRAIR7-61-P2/1962), was
downloaded from the GISAID EpiPox™ da-
tabase 15 (Fig. 2). Viral genomic sequences
are the main pipeline of this study, but we
were also interested in connecting them
with other available epidemiological data
such as patient information: patient status,
age, gender, type of sample specimen, date
and location of origin of the MPXV isolates
therefore additionally TSV files with the
above-mentioned information were down-
loaded. The multi-FASTA file with nucleotide
sequences and the TSV file with the sam-
ples epidemiological metadata are linked
through the accession_id of the sequences.
With the TSV files with epidemiological
metadata from the GISAID EpiPox™ data-
base, a correlational analysis was performed
through an alluvial flow diagram, which rep-
resents the correlations between categori-
cal dimensions represented as a flow, visu-
ally connecting the shared categories. Each
rectangle of the categories represents a sin-
gle value in the selected dimension and its
height is proportional to the value. Curved
lines represent the correlations and their
weight is proportional to the values. The al-
luvial diagram was executed in RAWGraphs.
RAWGraphs is an open-source data visualiza-
tion framework built for the visual represen-
tation of complex data 16.
The multi-FASTA file of 940 complete
MXPV sequences downloaded from the GI-
SAID EpiPox™ database was first analysed
using the Monkeypox virus typing tool from
Genome Detective. Genome Detective is an
intuitive Bio-Informatics application for the
analysis of pathogenic microbial molecular
sequence data 17. Monkeypox virus typing
tool is designed to use BLAST and phylo-
genetic methods to identify the Monkeypox
virus lineages (all clades) of a nucleotide se-
quence. Genome Detective generates a re-
72 Moros et al.
Investigación Clínica 64(1): 2023
port with the specie assignment, subtyping,
and sequence length as a CVS file.
Subsequently, the genomic sequences
were analyzed in Nextclade (ver. 2.3.1)18.
Nextclade, is a web-tool that performs based
on Smith–Waterman alignment with an af-
fine gap-penalty, that identifies differences
between sequences and a reference sequence
used by Nextstrain, 18 an open-source proj-
ect to analyze pathogen genome data, to as-
sign clades, mutation callings, and sequence
quality 18. For monkeypox, analysis, the Mon-
keypox (all clades) algorithm was used with
a reference sequence of a reconstructed
ancestral sequence of MPXV reporting phy-
logenetic analysis. JSON and TSV files were
downloaded from Nextclade for gene tree
analysis. The JSON file containing the phy-
logenomic datasets was analysed at Auspice.
us 18. Auspice.us is a web-tool for interactive
exploration and visualizing phylogenomic
datasets, also used by Nextstrain. From Aus-
pice.us the files NEWICK and NEXUS were
downloaded for further analysis and editing
of the phylogenetic tree in iTOL (Interactive
Tree of Life) (ver. 6) 19. iTOL is a web-tool
for the visualization, annotation and man-
agement of phylogenetic trees including
clade distances 19. The phylogenetic tree was
downloaded in multiple formats (PDF, EPS,
and SVG) for final editing and formatting in
Illustrator CS (ver. 23.0.1).
A treemap graph and a sunburst dia-
gram were constructed in RawGraphs 20, to
analyze the proportion of genomic sequenc-
es and to identify the geographic distribu-
tion of lineages and sub-lineages, respec-
tively. The treemap is composed of an area
divided into small rectangles, representing
the tree structure’s last level based on the
proportion of the lineage and sub-lineages.
The size of the rectangles depends on the
quantitative dimension. The sunburst dia-
gram shows hierarchically structured data
and a related quantitative dimension by con-
centric circles. The centre circle represents
the root node (the continents), and the hi-
erarchies (the continents following by sub-
lineages) move outward from the center. The
angle of each arc corresponds to the qualita-
tive dimension.
RESULTS
MPXV sequences information
From April 1 to September 2, 2022, the
GISAID database contained a total of 1555
submitted MPXV sequences, of which only
web tools involved in this study from the se-
The flow starts by
collecting the complete MPXV sequence from
GISAID EpiPox™. Additionally, data on patient
status, date and place of origin of the MPXV
sequences were also downloaded. An alluvial
diagram was constructed in the RAWGraphs
web-tool. The sequences were submitted and
analyzed to Genome Detective and Nextclade.
The phylogenetic tree was constructed in Aus-
pice.us and edited in iTOL.
Monkeypox virus global outbreak 73
Vol. 64(1): 68 - 80, 2023
940 sequences were complete genome se-
quences with a high coverage; additionally,
including two reference sequences were in-
cluded. Most sequences were submitted be-
tween May 1 and August 31, 2022 (data not
shown).
In the period studied for this work, 30
countries have submitted sequences to the
GISAID Epipox™ database. In Europe, the
countries that have repositioned sequences
are: Finland, Sweden, France, Slovenia, Italy,
Austria, Netherlands, Portugal, UK, Germa-
ny, Spain, Hungary, Belgium and Slovakia.
From America: USA, Canada, Ecuador, Chile,
Brazil, Peru and Mexico. From Asia: South
Korea, Indonesia, Thailand, Japan, Taiwan,
Singapore and Israel. From Africa and Ocea-
nia: South Africa and Australia, respectively.
Inspection of the alluvial diagram for
patterns of the complete MPXV sequences
present in the EpiPox database shows that the
vast majority of the deposited sequences of
MPXV in EpiPox were from Europea (503 se-
quences - 53.51%), followed by America (423
sequences - 45%), and other sequences came
from Oceania, Africa, and Asia (Fig. 3). The
country with the highest number of sequenc-
es deposited in EpiPox™ is Germany (327 se-
quences – 34.78%), followed by USA, Canada,
Peru, UK, Brazil, Portugal, and Netherland.
The rest of the countries that have deposited
sequences have less than ten sequences (be-
tween 1–8 sequences).
Unfortunately, not all the complete
MPXV sequences have all the epidemiologi-
cal information, i.e., the vast majority of the
Fig. 3. Alluvial diagrams of the epidemiological information of the 940 complete GISAID EpiPox™ sequen-
ces. The alluvial diagram showing the correlations between categorical dimensions information flow
patterns of the 940 complete GISAID EpiPox™ sequences with high coverage. The categories corre-
lated were: A: continent, B: country, C: gender, D: age, and E: specimen (sample type origin). This
information comes from patients, from whom the MPXV strains were isolated.
74 Moros et al.
Investigación Clínica 64(1): 2023
patient’s gender is unknown (746 sequences
– 79.36%). In the cases where this data was
reported, the male gender corresponded to
the main gender (188 sequences – 20%),
while only six sequences were from female
patients (0.63%).
Regarding the origin of the specimens
of the MPXV sequences, most came from
related lesion origin (including crusts and
vesicles) (530 sequences – 56.38%). Other
types of specimens specified came from na-
sopharyngeal, buccal, blood, anal and genital
areas. For a large number of the specimens
the origen of the samples was unknown (364
sequences – 38.72%).
MPXV sequences phylogenetic assignation
Of the 940 sequences obtained in GI-
SAID EpiPox™, the Genome Detective web
tool assigned 937 (99.7%) as MPXV of the
clade II (Table 1) while identifying reference
sequences as Variola virus and one as Aba-
tino macacapox virus, both viruses affiliated
to the genus Orthopoxvirus.
The Maximum Likelihood Phylogenet-
ic tree of 940 whole genome sequences of
MPXV was developed as per definitions of
the GISAID clades using the Nextstrain algo-
rithm (Fig. 4). The overall clades, lineages,
and sub-lineages distribution were high-
lighted, revealing the dominant occurrence
of lineage B.1 following the nomenclature
proposed and described in Happi et al. [12]
and recently endorsed by a WHO convened
consultation [11]. The GISAID MPXV se-
quences were analyzed to characterize the
diversity of clade II. All sequences were as-
signed within clade II within sub-lineage B.1
regardless of continent or country of origin,
and only one sequence within sub-lineage
A.2 from Thailand.
Globally, most sequences studied
were assigned to the B.1 lineage of clade II
(54.14%) followed by the sub-lineages B.1.1
(15%)> B.1.2 (7.55%)> B.1.6 (7.44%)>
B.1.7 (5.10%)> B1.3 (3.9%)> B.1.4
(2.34%)> B.1.8 (2.23%)> B.1.5 (2.12%)>
A.2 (0.1%) (Fig. 5A). Within countries, the
distribution is similar to the overall inci-
dence observed, i.e., B.1 prevails as the pre-
dominant lineage followed by sub-lineage
B.1.1., in almost all the countries with some
exceptions (Slovenia: B.1.3, Italy: B.1.5,
Peru B.1.6, and Thailand: A.2) (Fig. 5.B).
DISCUSSION
During a large-scale pandemic with an
exponential spread such as COVID-19, re-
search data have become an extremely im-
portant resource, especially regarding ge-
nomic surveillance of SARS-CoV-2. There
are now several possibilities for sharing ge-
nomic sequences from research and diag-
nostics. Among the initiatives to share this
type of data for biomedical researchers is
the GISAID repository. The COVID-19 global
health emergency has shown that to acceler-
ate research and control of these infections,
research data must be shared rapidly and
widely, allowing many published epidemio-
logical studies to be developed solely from
open research data 21.
MPXV is a neglected infectious patho-
gen and has re-emerged unexpectedly dur-
ing the COVID-19 pandemic, becoming an
Table 1
Samples genotype assignment.
Blast assignment Genotype assignment Sequences count Percentage
Abatino macacapox virus Not assigned 1 0.106%
Monkeypox virus Clade II 937 99.7%
Variola virus Not assigned 2 0.213%
Total 940 100%
Monkeypox virus global outbreak 75
Vol. 64(1): 68 - 80, 2023
Fig. 4. Phylogeny analysis of MPXV 2022-year outbreak. Phylogeny analysis of MPXV using 940 genome
sequences from GISAID EpiPox™, plus two reference sequences. The circular phylogenetic tree is divi-
ded into clades. Clade II was divided by the group and sub-groups linages: hMPXV 1.A, A.1, A.2, A.1.1
and B.1 identified by NextStrain code colour. Sequence colours were identified by each continent
origin and grey colour for reference sequences.
Fig. 5. Proportion and geographic distribution of MPXV Clade II lineages and sub-lineages. A: Treemap gra-
ph based on the proportion of the clade II lineage and sub-lineages. B: Sunburst diagram showing hie-
rarchically nodes (the continents, countries and lineage and sub-lineages). Lineages and sub-lineage
colour by NextStrain code colour.
76 Moros et al.
Investigación Clínica 64(1): 2023
outbreak of global concern to the worldwide
health burden. As of June 2022, more than
75 countries have detected this virus; more
than 55,000 confirmed cases had been con-
firmed, making it the largest outbreak out-
side of Africa since its discovery in the 1970s.
The rapid spread of this virus is evidenced by
the fact that they are travel-related 22.
In this study, we used the information
deposited in the GISAID EpiPox™ database
uploaded during April and September, 2022
and analyzed it using different web-tools. The
vast majority of the sequences retrieved from
GISAID are from the European continent,
probably due to the center and origin of this
MPXV outbreak later spreading mainly to the
American continent. In addition, most samples
were derived from male gender patients. These
results are consistent with early-published re-
ports of the MPXV outbreak 23.
Our analysis shows that the sequences
recovered from the GISAID EpiPox™ data-
base from the recent outbreak of monkeypox
in several countries, wich initiated in April
2022, are derived from the B.1 monkeypox
clade II. These results are similar to earlier-
published reports 24–29, consistent with the
reported mild severity and few deaths associ-
ated with the clade II 30,31.
Interestingly, sequences from only 30
countries have been deposited in GISAID in
the period covered in this work. This con-
trasts the global data where at least 100
countries and territories with confirmed
cases of MPXV have been reported 32. No-
tably, only five sequences from Spain were
found for our analysis, a country with almost
7000 cases reported. Moreover, although
cases have been reported in several African
countries such as Cameroon, Central Afri-
can Republic, Democratic Republic of the
Congo, Ghana, Liberia, Nigeria, Republic of
the Congo, no sequences from those coun-
tries were found in the database. Only two
sequences were obtained from South Africa,
a country that, like the rest of the countries
analyzed in this study, has not historically re-
ported monkeypox cases 32.
In Latin America, the sequences sub-
mitted by Peru indicate a different behav-
ior with respect to the rest of the countries
on the American continent. Most Peruvian
sequences were assigned to B.1.6., a new
lineage identified in the South American
country and characterized by the nucleotide
mutation G111029A 33. This specific type
of mutation is characteristic of the action
of the APOBEC3 family of deaminases. This
enzyme acts on single-stranded DNA to de-
aminate cytosine to uracil, causing a G→A
mutation on the other strand when it is
newly synthesized 34,35. It has been reported
that APOBEC3G in vif-defective HIV-1 virus,
APOBEC molecules are packaged into the vi-
rion and induce large numbers of mutations
35,36. APOBEC3 type mutations have been ob-
served within eight genomes sampled from
an outbreak in Portugal 25,37.
The appearance of new sub-lineages in
such a short period (April-September, 2022)
indicates the rapid evolution and dynamics
of this virus, possibly due to the changes
generated by the spread of the virus outside
the African continent where it was confined.
However, further genetic, molecular, and
perhaps external factors, such as environ-
mental and human societal habits, need to
be studied to understand better how MPXV
evolves.
GISAID database publicly accessible da-
tabase has allowed collaboration among re-
searchers around the world to contribute to
the understanding of the development and
evolution of the SARS-CoV-2 pandemic and
its impact on global public health. As well as
access to near real-time variant emergence
and key mutations and understanding the
pathogenesis of the viruses, it has contrib-
uted to the study and development of po-
tential new vaccines and drugs 38,39. GISAID
EpiPox™ database is also expected to play
a significant role in the surveillance of this
new global outbreak of MPXV. However, it is
essential to overcome the difficulties of col-
lecting epidemiological data, to have a bet-
ter and complete epidemiological landscape
Monkeypox virus global outbreak 77
Vol. 64(1): 68 - 80, 2023
that will improve the monitoring of the cur-
rent outbreak of MPXV.
ACKNOWLEDGEMENTS
We gratefully acknowledge the authors,
curators, and submitters from the originat-
ing and submitting laboratories of the MPXV
genomic sequences from GISAID EpiPox™
Database on which this research is based,
a full acknowledgment table for all GISAID
authors can be downloaded at https://bit.
ly/3wWZ1Hb. We also acknowledge GISAID
initiative, Genome Detective, Nexstrain,
Nextclade, Auspice.us, iTOL, and RAW-
Graphs web tool resources used in this study.
Funding
This project was funded by project
IVIC#1107: Viral pathogenesis mechanisms.
Conflict of Interest Statement
The authors declare that they have no
conflicts of interest.
Author’s ORCID numbers
• Zoila C Moros (CZM)
0000-0001-6322-9230
• Carmen L Loureiro (CLL)
0000-0003-3665-1107
• Rossana C Jaspe (RCJ)
0000-0002-4816-1378
• Mariangel Delgado (MD)
0000-0002-8089-5873
• Olga Carolina Aristimuño (OCA)
0000-0001-7646-8302
• Christopher Franco (CF)
0000-0002-1851-1226
• Yoneira Sulbarán (YS)
0000-0002-3170-353X
• Domingo J Garzaro (DJG)
0000-0002-9956-5786
• Mariajosé Rodríguez (MR)
0000-0002-8898-0546
• Héctor R Rangel (HRR)
0000-0001-5937-9690
• Ferdinando Liprandi (FL)
0000-0001-8084-8252
• Flor H Pujol (FHP)
0000-0001-6086-6883
• José Luis Zambrano (JLZ)
0000-0001-9884-2940
Authors contribution
Design of the study: JLZ. Implemen-
tation of the research and writing of the
manuscript: JLZ, ZCM, CLL, RCJ, and FHP.
Discussed the results and contributed to the
final manuscript: ZCM, CLL, RCJ, YS, MD,
OCA, CF, MH, DJG, MR, HRR, FL, FHP, and
JLZ. Data visualization: JLZ. All the authors
have read and approved the final version of
the manuscript. ZCM and CLL contributed
equally to this study.
REFERENCES
1. World Health Organization (WHO). Mee-
ting of the International Health Regulations
(2005) Emergency Committee regarding
the multi-country monkeypox outbreak.
Accessed July 22, 2022. https://www.who.
int/news/item/25-06-2022-meeting-of-the-
international-health-regulations-(2005)-
emergency-committee--regarding-the-mul-
ti-country-monkeypox-outbreak
2. Prier JE, Sauer RM. A Pox Disease of Monkeys.
Ann N Y Acad Sci 1960;85(3):951-959.
doi:10.1111/J.1749-6632.1960.TB50 015.X.
3. Monkeypox: A new
treat? Int J Mol Sci 2022;23(14):7866.
doi:10.3390/IJMS23147866
4.
Monkeypox Virus in Nigeria: infection bio-
logy, epidemiology, and evolution. Viruses
2020;12(11):1257. doi:10.3390/V12111257
5. Monkeypox virus: a
neglected zoonotic pathogen spreads glo-
bally. Nat Rev Microbiol Published online
78 Moros et al.
Investigación Clínica 64(1): 2023
July 20, 2022:1. doi:10.1038/S41579-022-
00776-Z
6. -
. Here, there, and
everywhere: the wide host range and geo-
graphic dstribution of zoonotic orthopoxvi-
ruses. Viruses 2020;13(1):43. doi:10.3390/
V13010043
7.
-
When a neglec-
ted tropical disease goes global: knowledge,
attitudes and practices of Italian pysi-
cians towards monkeypox, preliminary re-
sults. Trop Med Infect Dis 2022;7(7):135.
doi:10.3390/TROPICALMED7070135
8. -
-
-
. Extended human-to-
human transmission during a Monkeypox
outbreak in the Democratic Republic of the
Congo. Emerg Infect Dis 2016;22(6):1014.
doi:10.3201/EID2206.150579
9. Monkey-
pox: another sexually transmitted infection?
Pathogens 2022;11(7):713. doi:10.3390/
PATHOGENS11070713
10. -
Phylogenomic analysis of the monkey-
pox virus (MPXV) 2022 outbreak: Emer-
gence of a novel viral lineage? Travel Med
Infect Dis 2022;49:102402. doi:10.1016/J.
TMAID.2022.102402
11. World Health Organization (WHO). Monke-
ypox: experts give virus variants new names.
Accessed September 5, 2022. https://www.
who.int/news/item/12-08-2022-monkey-
pox--experts-give-virus-variants-new-names
12.
-
-
. Urgent need
for a non-discriminatory and non-stigma-
tizing nomenclature for monkeypox virus
- Monkeypox - Virological. Accessed Sept-
ember 5, 2022. https://virological.org/t/
urgent-need-for-a-non-discriminatory-and-
non-stigmatizing-nomenclature-for-monke-
ypox-virus/853
13. -
Genomic annota-
tion and molecular evolution of monkeypox
virus outbreak in 2022. J Med Virol Pu-
blished online July 29, 2022. doi:10.1002/
JMV.28036
14. -
Role
of genomics in combating COVID-19 pande-
mic. Gene 2022;823:146387. doi:10.1016/J.
GENE.2022.146387
15. Data, disease
and diplomacy: GISAID’s innovative contri-
bution to global health. Global Challenges
2017;1(1):33-46. doi:10.1002/GCH2.1018
16.
M. RAWGraphs: A visualisation platform to
create open outputs. ACM International
Conference Proceeding Series. 2017;Part
F131371. doi:10.1145/3125571.3125585
17.
-
Genome Detec-
tive: an automated system for virus identi-
fication from high-throughput sequencing
data. Bioinformatics 2019;35(5):871-873.
doi:10.1093/BIOINFORMATICS/BTY695
18.
NextStrain: Real-time trac-
king of pathogen evolution. Bioinforma-
tics 2018;34(23):4121-4123. doi:10.1093/
BIOINFORMATICS/BTY407
19. Interactive tree of life
(iTOL) v5: An online tool for phylogenetic
tree display and annotation. Nucleic Acids
Res 2021;49(W1):W293-W296. doi:10.1093/
NAR/GKAB301
20.
M. RAWGraphs: A visualisation platform to
create open outputs. ACM International
Conference Proceeding Series. 2017;Part
F131371. doi:10.1145/3125571.3125585
Monkeypox virus global outbreak 79
Vol. 64(1): 68 - 80, 2023
21.
. The sharing
of research data facing the COVID-19 pan-
demic. Scientometrics 2021; 126(6):4975.
doi:10.1007/S11192-021-03971-6
22.
Travel-related Monkeypox outbreaks in the
era of COVID-19 pandemic: are we prepa-
red? Viruses 2022;14(6):1283. doi:10.3390/
V14061283
23. World Health Organization (WHO). Multi-
country monkeypox outbreak: situation
update. Accessed August 1, 2022. https://
www.who.int/emergencies/disease-out-
break-news/item/2022-DON393
24.
-
Reynolds MG. Exportation of Monkeypox
Virus from the African continent. J Infect
Dis 2022;225(8):1367-1376. doi:10.1093/
INFDIS/JIAA559
25. -
-
-
Belgian case
of Monkeypox virus linked to outbreak in
Portugal - Monkeypox / Genome Reports
- Virological. Accessed August 2, 2022.
https://virological.org/t/belgian-case-of-
monkeypox-virus-linked-to-outbreak-in-por-
tugal/801
26. -
First draft genome sequence of Monke-
ypox virus associated with the suspected
multi-country outbreak, May 2022 (con-
firmed case in Portugal) - Monkeypox /
Genome Reports - Virological. Accessed
August 2, 2022. https://virological.org/t/
first-draft-genome-sequence-of-monkeypox-
virus-associated-with-the-suspected-multi-
country-outbreak-may-2022-confirmed-ca-
se-in-portugal/799
27.
Reyes M. Monkeypox virus genome sequence
from an imported case in Colombia - Monke-
ypox / Genome Reports - Virological. Acces-
sed August 2, 2022. https://virological.org/t/
monkeypox-virus-genome-sequence-from-an-
imported-case-in-colombia/880
28. -
-
-
macho-Ortiz A. First Monkeypox virus se-
quence from northern Mexico - Monkeypox
/Genome Reports - Virological. Accessed
August 2, 2022. https://virological.org/t/
first-monkeypox-virus-sequence-from-nor-
thern-mexico/882
29.
A. Two draft Canadian monkeypox virus
(MPXV) genomes, June 2022 - Monkeypox
/ Genome Reports - Virological. Accessed
August 2, 2022. https://virological.org/t/
two-draft-canadian-monkeypox-virus-mpxv-
genomes-june-2022/870
30.
K. Human monkeypox outbreak in 2022.
J Med Virol Epub 2022 Jun 6. doi:10.1002/
JMV.27894
31. World Health Organization (WHO). Multi-
country monkeypox outbreak: situation
update. Accessed August 2, 2022. https://
www.who.int/emergencies/disease-out-
break-news/item/2022-DON390
32. Centers for Disease Control and Preven-
tion (CDC). 2022 Monkeypox Outbreak
Global Map | Monkeypox | Poxvirus | CDC.
Accessed September 6, 2022. https://
www.cdc.gov/poxvirus/monkeypox/respon-
se/2022/world-map.html
33. Peru identifies
monkeypox virus B.1.6 lineage - Outbreak
News Today. Accessed September 6, 2022.
https://web.ins.gob.pe/
80 Moros et al.
Investigación Clínica 64(1): 2023
34. Initial observa-
tions about putative APOBEC3 deamina-
se editing driving short-term evolution of
MPXV since 2017 - Monkeypox / Evolution
- Virological. Accessed September 6, 2022.
https://virological.org/t/initial-observa-
tions-about-putative-apobec3-deaminase-
editing-driving-short-term-evolution-of-
mpxv-since-2017/830#post_1
35.
Single-strand specificity of APOBEC3G
accounts for minus-strand deamination
of the HIV genome. Nat Struct Mol Biol
2004;11(5):435-442. doi:10.1038/NSMB758
36.
-
Conserved footprints of APOBEC3G
on Hypermutated human immunodeficien-
cy virus type 1 and human endogenous
retrovirus HERV-K(HML2) sequences. J Vi-
rol 2008;82(17):8743-8761. doi:10.1128/
JVI.00584-08
37.
-
Phylogenomic characterization and
signs of microevolution in the 2022 multi-
country outbreak of monkeypox virus. Nat
Med 2022;28(8). doi:10.1038/S41591-022-
01907-Y
38. -
Covid-19
and Artificial Intelligence: Genome sequen-
cing, drug development and vaccine disco-
very. J Infect Public Health 2022;15(2):289.
doi:10.1016/J.JIPH.2022.01.011.
39. Construction of
epitope-based peptide vaccine against SARS-
CoV-2: Immunoinformatics study. J Pure
Appl Microbiol 2020;14(Suppl1):999-1005.
doi:10.22207/JPAM.14.SPL1.38.
