**1. Introduction and background**

The Ebola virus was first discovered back in 1976 when its breakout occurred simultaneously in South Sudan and in the area of Ebola River in Yambuku city of Democratic Republic of Congo (**Figure 1**) [1]. It reemerges in 1990s, 2000s, peaked in 2014 and 2018–2019 (**Figure 1**). This RNA viral disease caused hemorrhagic fever in humans and non-human primates [2]. The African originated species of Ebola virus fatality rate in humans is nearly 90% [2]. Ebola, Marburg, and Cueva virus are the three infectious viruses with a common ancestor of the family Filoviridae [2]. The word "filo" in Filoviridae is derived from the Latin word film, which means thread like, as these virions appear thread-like under the electron microscope [3]. The Filoviridae family is part of the order Mononegavirales, class Monjiviricetes and phylum Negarnaviricota in the virus taxonomic classification [4, 5]. Ebola, also known as Ebola virus disease (EVD/EBOV) and Ebola hemorrhagic fever (EHF) in the past, is a filamentous, enveloped, non-segmented, single stranded negative sense ribonucleic acid (RNA) virus [4]. The replication of Filoviridae family of viruses takes place in the cytoplasm of the host cell [6, 7]. The genomic RNA is non-contagious alone because it is not able to serve as a template for protein synthesis [6, 7]. To start the transcription of positive-sense messenger RNA (mRNA) the viral protein must connect with the genomic RNA [6, 7].

**Figure 1.**

*Reported cases and deaths from EBOV in different countries from 1976 to 2014 according to WHO [8].*

The objective of this work is to provide firsthand information regarding the EBOV origin, infection, control and progress in vaccine development.

#### **1.1 Origin**

The Ebola virus is taxonomically classified into five species. These species includes Zaire Ebola virus (EBOV), Reston Ebola virus (RESTV), Taï Forest Ebola virus (TAFV) or Coted'Ivoire Ebola virus (CIEBOV) [9], Sudan Ebola virus (SUDV), and Bundibugyo Ebola virus (BDBV) [10]. Four of these species are responsible to cause disease in humans and one in nonhuman primates [10]. The species of Ebola viruses are named from where they originated for the first time [11]. The BDBV was first found in 2007 in Bundibugyo district of Uganda with 116 cases and fatality rate of 25% [12, 13]. RESTV emerged in 1989 in Reston (Virginia), USA, causing diseases in nonhuman primates [14, 15]. SUDV was first discovered in 1976 in a cotton factory in South Sudan (Nzara). Its mortality rate varies from 53 to 68%. The mortality rate is the death rate due to certain disease in a particular population. CIEBOV (Tai forest virus) was first reported in 1994. The virus appeared in chimpanzees in Africa in Tai forest [16]. ZEBOV has the highest lethality rate up to 90%, which includes the first appeared virus and the most current outbreak [17].

#### **1.2 History**

The Ebola virus is named after a small river, Ebola in Zaire and this viral infection first appeared in 1976 in both South Sudan and Zaire in the African continent [18–20]. The international teams of WHO reached the affected area but were unsuccessful in saving more lives and collecting vital information due to lack of medical facilities and illiteracy in rural areas [21]. This virus family becomes genetically more advanced and spread into other areas, and appeared in the united states in 1989 [22]. EBOV did not appear in Africa for 15 years but as the natural reservoir

**55**

*Ebola, the Negative Stranded RNA Virus DOI: http://dx.doi.org/10.5772/intechopen.91776*

**1.3 Transmission, symptoms, and treatment**

EBOV infected patients.

simultaneously [33].

**1.4 EBOV genomic organizations**

maintained to the normal level.

provided to control the blood loss.

d.The patient should increase the intake of fluids.

was not completely eliminated and due to this reason the virus showed itself again in 1994–1996 [23]. During 1994–1996, the new subtype of Ebola Coted'Ivoire was discovered, while the old subtypes were also present. The people infected were living near the tropical forest area. The ethnologist's discovered that the fifth subtype was found in the chimpanzee group with a high fatality rate. They were transferred to Switzerland for suitable facilities and medical care by a group of scientists [24]. The outbreak in 2014 has the highest fatality rates in the history of EBOV [25].

EBOV is a rare and deadly disease caused by infection with one of the Ebola virus strains. Humans and non-human primates are the primary hosts of Ebola [26]. The different types of insectivorous bat genus, especially *Mops condylurus* and frugivorous bat species are also the host of EBOV [27–29]. The fruits eating bat is also a common reservoir of ebola virus [30, 31]. The virus is transmitted through contaminated blood and bodily fluids of infected person or animal. Fever, muscle ache, loss of appetite, and fatigue are the common symptoms after onset of EBOV, while in fatal cases, severe vomiting, diarrhea, hemorrhage, septic shock, and multi-organ failure may occur that may lead to death in 30–90% patients [32]. The patients can be treated as the symptoms of EBOV appear in them. Currently, there is no proper Federal Drug Authority (FDA) approved medicines or vaccines. The following are some of the interventions and precautions for survival against EBOV;

a.Intravenous fluids (IV) and body salts should be regularly provided to the

b.The blood pressure and oxygen status of patients should be monitored and

c.The blood lost during the illness should be replaced and medicines should be

e.The other infections which develop during treatment should also be treated

The EBOV genome has nucleotide sequences which are extragenic. The sequences combine to produce secondary structures that contain 3′ and 5′ ends. The genome serves to initiate transcription and genome replication [34, 35]. The negative-stranded RNA genome of EBOV contains seven important genes that are arranged in a linear fashion and has a total length of approximately 19 kilobases and it translated into eight proteins [36]. Its sequence is as follows 3′-NP, VP35, VP40, GP, VP30, VP24, L-5′as shown in **Figure 2**. The VP (35) is RNA-dependent RNA polymerase cofactor, VP(40) is a matrix protein, GP(1,2) is spike glycoprotein, VP(30) is a transcriptional activator, VP (24) is the second protein matrix and (L) is RNA polymerase enzyme [6]. The RNA genome of the virus is coated by a complex of ribonuclear protein (RNP). It is also known as nucleocapsid. The nucleocapsid is composed of major nucleoprotein (NP), minor nucleoproteins that include VP(30), VP(35), and polymerase (L) protein as shown in **Figure 3** [37, 38]. The above complex is then enveloped in a layer of matrix. The matrix consists of

*Ebola, the Negative Stranded RNA Virus DOI: http://dx.doi.org/10.5772/intechopen.91776*

*Some RNA Viruses*

The objective of this work is to provide firsthand information regarding the EBOV

*Reported cases and deaths from EBOV in different countries from 1976 to 2014 according to WHO [8].*

The Ebola virus is taxonomically classified into five species. These species includes Zaire Ebola virus (EBOV), Reston Ebola virus (RESTV), Taï Forest Ebola virus (TAFV) or Coted'Ivoire Ebola virus (CIEBOV) [9], Sudan Ebola virus (SUDV), and Bundibugyo Ebola virus (BDBV) [10]. Four of these species are responsible to cause disease in humans and one in nonhuman primates [10]. The species of Ebola viruses are named from where they originated for the first time [11]. The BDBV was first found in 2007 in Bundibugyo district of Uganda with 116 cases and fatality rate of 25% [12, 13]. RESTV emerged in 1989 in Reston (Virginia), USA, causing diseases in nonhuman primates [14, 15]. SUDV was first discovered in 1976 in a cotton factory in South Sudan (Nzara). Its mortality rate varies from 53 to 68%. The mortality rate is the death rate due to certain disease in a particular population. CIEBOV (Tai forest virus) was first reported in 1994. The virus appeared in chimpanzees in Africa in Tai forest [16]. ZEBOV has the highest lethality rate up to 90%, which includes

The Ebola virus is named after a small river, Ebola in Zaire and this viral infection first appeared in 1976 in both South Sudan and Zaire in the African continent [18–20]. The international teams of WHO reached the affected area but were unsuccessful in saving more lives and collecting vital information due to lack of medical facilities and illiteracy in rural areas [21]. This virus family becomes genetically more advanced and spread into other areas, and appeared in the united states in 1989 [22]. EBOV did not appear in Africa for 15 years but as the natural reservoir

origin, infection, control and progress in vaccine development.

the first appeared virus and the most current outbreak [17].

**54**

**1.1 Origin**

**Figure 1.**

**1.2 History**

was not completely eliminated and due to this reason the virus showed itself again in 1994–1996 [23]. During 1994–1996, the new subtype of Ebola Coted'Ivoire was discovered, while the old subtypes were also present. The people infected were living near the tropical forest area. The ethnologist's discovered that the fifth subtype was found in the chimpanzee group with a high fatality rate. They were transferred to Switzerland for suitable facilities and medical care by a group of scientists [24]. The outbreak in 2014 has the highest fatality rates in the history of EBOV [25].

### **1.3 Transmission, symptoms, and treatment**

EBOV is a rare and deadly disease caused by infection with one of the Ebola virus strains. Humans and non-human primates are the primary hosts of Ebola [26]. The different types of insectivorous bat genus, especially *Mops condylurus* and frugivorous bat species are also the host of EBOV [27–29]. The fruits eating bat is also a common reservoir of ebola virus [30, 31]. The virus is transmitted through contaminated blood and bodily fluids of infected person or animal. Fever, muscle ache, loss of appetite, and fatigue are the common symptoms after onset of EBOV, while in fatal cases, severe vomiting, diarrhea, hemorrhage, septic shock, and multi-organ failure may occur that may lead to death in 30–90% patients [32]. The patients can be treated as the symptoms of EBOV appear in them. Currently, there is no proper Federal Drug Authority (FDA) approved medicines or vaccines. The following are some of the interventions and precautions for survival against EBOV;


#### **1.4 EBOV genomic organizations**

The EBOV genome has nucleotide sequences which are extragenic. The sequences combine to produce secondary structures that contain 3′ and 5′ ends. The genome serves to initiate transcription and genome replication [34, 35]. The negative-stranded RNA genome of EBOV contains seven important genes that are arranged in a linear fashion and has a total length of approximately 19 kilobases and it translated into eight proteins [36]. Its sequence is as follows 3′-NP, VP35, VP40, GP, VP30, VP24, L-5′as shown in **Figure 2**. The VP (35) is RNA-dependent RNA polymerase cofactor, VP(40) is a matrix protein, GP(1,2) is spike glycoprotein, VP(30) is a transcriptional activator, VP (24) is the second protein matrix and (L) is RNA polymerase enzyme [6]. The RNA genome of the virus is coated by a complex of ribonuclear protein (RNP). It is also known as nucleocapsid. The nucleocapsid is composed of major nucleoprotein (NP), minor nucleoproteins that include VP(30), VP(35), and polymerase (L) protein as shown in **Figure 3** [37, 38]. The above complex is then enveloped in a layer of matrix. The matrix consists of

the major and minor matrix protein VP40, VP24, respectively. Then, the matrix proteins are encapsulated by a double layer of lipid which is then peppered with the viral glycoprotein (GP) that help in binding to the host cell [39, 40]. All five EBOV species discovered so far has the same GP gene organization which is divided into sGP, GP1, GP2, and ssGP [41, 42].

#### **Figure 2.**

*Important proteins in the RNA genome of EBOV [43].*

#### **Figure 3.**

*The virion structure showing the nuclear material and glycoproteins [44].*

### **1.5 Structure of glycoproteins**

It has been observed that most of the viral components play an active role in the pathogenesis and infection of this viral disease, but the major role is played by the glycoproteins of the EBOV [45]. Thus, they possess a significant importance in the virulence of EBOV and targeting its synthesis is one of important step for controlling this infection [45]. EBOV includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. Each gene product

**57**

**Figure 4.**

*Biosynthesis of glycoproteins of EBOV [45].*

*Ebola, the Negative Stranded RNA Virus DOI: http://dx.doi.org/10.5772/intechopen.91776*

**1.6 Production of glycoproteins**

*1.7.1 Small secreted glycoprotein of EBOV*

infection:

linked covalently to the polypeptide chain [48].

has distinct biochemical and biological properties [46, 47]*.* The fourth gene, GP is formed by a process known as glycosylation in which carbohydrate are

host cell membrane [49]. The flowchart is shown in **Figure 4** [45].

**1.7 Classification and functions of EBOV glycoproteins**

The biosynthesis of glycoproteins occurs by transcription and expression strategies. The precursor of the secreted glycoproteins and full length glycoproteins are the initial products of EBOV glycoprotein. Pre-sGP is transcripted and translated to soluble products sGP and ∆-peptide while glycoprotein GP1, 2 is cleaved to GP1 and GP2. These two fragments are linked together by disulfide-bonding (S▬S). The GP1 helps in binding to the host cell and has a crucial role of EBOV entry across the

The Ebola virus actually produces the following soluble glycoproteins during

Small secreted glycoprotein (ssGP) is translated from part of mRNA. It is nonstructural and generated when two adenosines are combined or one is deleted during transcription [50]. The ssGP has monomeric structure which has identical 295 amino acids from starting point with secreted GP and full length GP but they vary at the C-terminus of the full length glycoprotein [51]. The host ADAM17 metalloprotease enzyme is responsible to generate ssGP. The antibodies that neutralize the viral glycoproteins are quickly blocked by the secreted complex GP [14]. This complex plays a key function in the virus pathogenesis. In spite of extensive necrosis and massive virus production, it therefore contributes to less inflammatory

reaction seen during the infection [14]. When the EBOV enters the host cell,

has distinct biochemical and biological properties [46, 47]*.* The fourth gene, GP is formed by a process known as glycosylation in which carbohydrate are linked covalently to the polypeptide chain [48].
