# Nihal Mine KANAR **Poxviruses** "Essential Human Virology by Jennifer Louten (2016)." Chapter 15 Pages: 273-290 link below
https://www.sciencedirect.com/book/9780128009475/essential-human-virology
Poxviruses are a complex family of dsDNA viruses that infect both vertebrates and invertebrates. Poxviruses got their name because of the visible lesions caused by the viruses.

Smallpox is one of the deadliest plagues in human history. Smallpox rash caused survivors to leave blind or visibly scarring throughout their lives, including on their faces (Figure 1). Variola virus (VARV), the virus that causes smallpox, is thought to have killed more people in history than any other infectious disease combined.

***Figure 1 Smallpox rash***

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# Taxonomy
The Poxviridae family includes 38 viruses that together infect a wide range of hosts that are mammals, birds, reptiles, and insects. The family contains two subfamilies, Chordopoxvirinae and Entomopoxvirinae (Table 15.1).


:::danger
VARV is the only orthopoxvirus that only infects humans. There are two different types of VARV: Variola major and Variola minor.
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**Orthopoxvirus characteristics**

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# Clinical Course of Variola Infection

**Clinical course of smallpox infection**

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**Frequency of Symptoms Observed With Smallpox Infection**

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**Characteristics of the Smallpox Rash**
:::info
(A) The centrifugal rash is characterized by lesions that are more prevalent on the extremities and face, as seen in this photograph of a Bengali boy with variola major. (Courtesy of CDC/Jean Roy.) (B) This girl with confluent smallpox has lesions on her arm that possess visible umbilications. (Courtesy of CDC/James Hicks.) (C) A depigmented scar remains after crusts separate, as seen on this Indonesian man recovering from smallpox. (Courtesy of CDC/Dr. J.D. Millar.)
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# Poxvirus Replication Cycle
Poxviruses are enveloped, brick-shaped viruses with dimensions of approximately 350 nm x 250 nm (Figs. 2A ans B). It is placing them among the largest human viruses.
***Figure 2 Molecular characteristics of orthopoxviruses

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**The two infectious forms of vaccinia virus**
:::info
Poxviruses have two infectious forms. The mature virion (A) possesses a dumbbellshaped core that encloses the dsDNA genome and several viral proteins. Over 20 proteins are associated with the surrounding lipid envelope. The enveloped virion (B) possesses an additional external membrane with a different complement of at least nine viral proteins. Mature virions are very stable and are thought to be involved in dissemination between hosts, while the fragile extra envelope of enveloped virions result in a virion that is better suited for infection within a single host.
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**Entry of vaccinia virus into the cell**

The attachment of the vaccinia virus differs depending on the virion type. After binding to cell surface molecules (1), the EV has proteins in its outer membrane, including proteins A34 and B5, that cause the outer membrane (2) to dissolve and release MV. MV has at least seven membrane proteins that facilitate attachment. Some of these bind to the surface glycosaminoglycans chondroitin sulfate and heparan sulfate, while others bind to membrane-associated proteins such as MARCO and laminin (3). The entry fusion complex of viral proteins connects the viral envelope with the plasma membrane (4), allowing the nucleus to enter the cytosol of the cell.

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# Viral Protein Expression and Genome Replication
Following fusion of the virion with the plasma or endosomal membrane, the nucleus travels deeper into the cell to a separate location outside the nucleus using microtubules. Moreover, a virus factory is formed, surrounded by membranes of the endoplasmic reticulum (Fig. 3).

***Figure 3 Poxvirus virus factory***

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**Poxvirus DNA replication**

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# Assembly, Maturation, and Release
VACV goes through various stages of virion morphogenesis, meaning the development of its shape (Fig. 4.A). The first visible indication of virus assembly is the existence of crescent membranes derived from the endoplasmic reticulum. Over nine viral membrane mounting proteins are required for the formation of crescent membranes (Fig. 4.B).
***Figure 4 Virion morphogenesis and release***

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# Eradication of Smallpox

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# Origin of Smallpox Vaccination
Edward Jenner created the first vaccine in 1796, when he tested and promoted the use of cowpox injections to confer immunity against smallpox.
**Portrait of Edward Jenner, M.D**

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# Modern Attempts at Smallpox Eradication
**Bifurcated needle (Courtesy of CDC / James Gathany)**

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**Last cases of variola minor and variola major**
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(A) Ali Maow Maalin had the last known cases of smallpox in the world, in Somalia in 1977. It was variola minor. The last case of variola major occurred in a child named Rahima Banu, in Bangladesh in 1975 (B).
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# Cessation of Smallpox Vaccination

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**Potential complications of the smallpox vaccine**
:::danger
Inadvertent autoinoculation (A)
Generalized vaccinia (B)
Progressive vaccinia or vaccinia necrosum (C)
Eczema vaccinatum (D)
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**Figure 5 Monkeypox**
:::warning
In humans, monkeypox virus causes symptoms that are clinically indistinguishable from smallpox (Fig. 5), with the addition of lymphadenopathy.
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Another interesting consequence of discontinuing vaccination is the potential for other smallpox viruses to infect humans. Monkeypox virus, a VARV-related orthopox virus, infects a wide variety of mammals, including humans. Smallpox vaccine has been shown to be at least 85% effective in preventing monkey disease due to the same cross-reactivity principles that lead to protection against VARV.

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