In Vitro Abortion

Clinical Question: Does HPV vaccination in MSM significantly prevent anogenital neoplasia occurrence and recurrence compared to not being vaccinated?

HPV lives in the body’s flat and thin cells on the skin’s surface called epithelial cells (“Information About the Human Papillomavirus”). There are more than 200 related viruses

As mentioned earlier, HPV is a non-enveloped, icosahedral capsid, double-stranded circular DNA virus (Morshed, 2014). Infection of HPV occurs in the cervix, glans of the penis, penile shaft, scrotom and anal verge by interactions with putative “host cell surface receptors such as heparin sulfate proteoglycans and alpha-6 integrins” Schafer, 2015; Letian, 2010). Most studies suggest that HPV16 enters the cell via clathrin-mediated endocytosis (Day, 2003, Bousarghin, 2003, Smith, 2007, Hindmarsh, 2007), however, notably, a few contradictory studies suggest that HPV16 is clathrin and caveolaen independent (Spoden, 2008). Once the virus has entered the cell, it then un-coats and delivers its genome (8 genes) to the host cell nucleus to be expressed. These eight genes are named for when they are expressed during the virus’s occupation of its host: early (E) and late (L). The proteins E1, E2, E4 and E5 play an important role in genome replication (Beutner, 1997; Gnanamony, 2007) while E6 and E7 are oncogenes and are capable of causing cancerous growth of host cell (Gnanamony, 2007; Sikorski, 1998). E6 is thought to complex with p53 which is a cellular tumor repressor (Werness, 1990); when E6 complexes with P53, it is thought to promote the degradation of p53 via the ubiquitin pathway (Schffner et al., 1990). This degradation of p53 contributes to the oncogenic potential of high-risk HPVs (Stewart, 2005, Thomas, 1999). Crook showed that E6 can bind with p53

Frequently, more recently in today’s society the disease known as HPV is a genital to genital disease that can be spread through sexual contact. The following

These IFNs induce an antiviral state in both the infected and neighboring cells, and prevent the spread of viral infections (41, 79). With a deficiency in type I or II signaling, host immune cells such as NK cells and neutrophils might not be able to function appropriately and therefore the host might be more susceptible to viral infection. However, Ifnk-/- and ifn-αβR- mice might be resistant to the MmuPV1 infection like NOD/SCID mice at cutaneous sites because of redundancy in these mice. Although it may seem disappointing but this finding will be worthy of additional investigation. Alternatively, we can test other mice deficient for critical IFN components such as MAVS, IRF-3, or IRF-7 that have shown increased morbidity and/or mortality to other viral infections (80). Other antiviral factors of innate immunity including human α- and β-defensins have been reported in HPV-associated anogenital warts (31, 32, 81, 82). We have detected downregulation of β-defensins 4 and 6 in MmuPV1-infected tissues by RNAseq (Table 1). We can explore whether these antiviral factors play a role in MmuPV1 infection. These additional studies will help to sort out the key players in papillomavirus

Human papillomavirus, commonly abbreviated as HPV, is the most common sexually transmitted virus that can cause a variety of diseases. It is transferred from person to person by either genital contact or from oral contact. Most men and women who are sexually active will be infected with this virus at least once in their life (“HPV”). A reason why HPV has become such a big problem in society is because of the fact that it is a virus, and thus cannot be treated with antibiotics. For other viral infections, it is possible to wait for the body’s immune system to rid the body of the foreign invader, but HPV is a virus that can cause more serious health problems such as genital warts, cancers of the mouth, anus, or vagina, as well as the cervix. Another reason why this problem exists in society may be due to more relaxed standards regarding sexual activity. In today’s society, people are more likely to have more than one sexual partner, making it easier for the virus to spread within the population. People are also becoming sexually active at younger ages before they receive education about safe sex at school or at home, which is also a factor in the spread of HPV in the population. Most people do not exhibit negative symptoms from the virus; indeed, some of them may not even know they have contracted it, for the body can clear out the virus on its own ninety percent of the time (“What is HPV?” 2013). HPV

As mentioned earlier, HPV is a non-enveloped, icosahedral capsid, double-stranded circular DNA virus (Morshed, 2014). Infection of HPV occurs in the cervix, glans of the penis, penile shaft, scrotom and anal verge by interactions with “host cell surface receptors such as heparin sulfate proteoglycans and alpha-6 integrins” (Schafer, 2015; Letian, 2010). Most studies suggest that HPV16 enters the cell via clathrin-mediated endocytosis (Day, 2003, Bousarghin, 2003, Smith, 2007, Hindmarsh, 2007), however, notably, a few contradictory studies suggest that HPV16 is clathrin and caveolaen independent (Spoden, 2008). Once the virus has entered the cell, it then un-coats and delivers its genome (8 genes) to the host cell nucleus to be expressed. These eight genes are named for when they are expressed during the virus’s occupation of its host: early (E) and late (L). The proteins E1, E2, E4 and E5 play an important role in genome replication (Beutner, 1997; Gnanamony, 2007) while E6 and E7 are oncogenes and are capable of causing cancerous growth of host cell (Gnanamony, 2007; Sikorski, 1998). E6 is thought to complex with p53 which is a cellular tumor repressor (Werness, 1990); when E6 complexes with P53, it is thought to promote the degradation of p53 via the ubiquitin pathway (Schffner et al., 1990). This degradation of p53 contributes to the oncogenic potential of high-risk HPVs (Stewart, 2005, Thomas, 1999). Crook (1991) showed that E6 can bind with p53 without degradation

Understanding of the HPV lifecycle is mainly derived from research on HPV 16. However, with slight modifications, life cycle model of HPV 16 can be applied to other HPV types as well.17 Skin to skin contact is the primary route of transmission, and sexual behavior greatly influences the incidence and prevalence of HPV infections.18 Virus finds its way to basal epithelial cell via micro-abrasions and micro-traumas on the skin. It is not fully understood how the virus binds with the surface of basal cells. However, L1 and L2 capsid proteins, alpha-6 integrin cellular receptors, and heparan sulfate proteoglycans/heparin sulfate may play a role in the process of binding.19 The virus enters basal epithelial cells through endocytosis, and the capsid is disassembled by the cellular endosome/lysosome. The L2 viral protein transfers the viral genome to nuclei of keratinocytes,20 and with the help of early viral proteins (E1 and E2), the virus maintains its episomal form and replicates in synchrony with the host DNA.17 As the infected host cells differentiate, late viral promoters are activated which facilitate viral packaging and release.17,20 Usually the expression of L1 and L2 viral proteins takes place in the granular layer the viral assembly in the cornified layer of the skin.7,20 Viruses are

As mentioned earlier, HPV is a non-enveloped, icosaheadral capsid, double-stranded circular DNA virus. Infection of HPV orccurs in the cervix, glans of the penis, penile shaft, scrotom and anal verge by interactive with putative host cell surface receptors such as heparin sulfate proteoglycans and alpha-6 integrins. Most studies suggest that HPV16 enters the cell via clathrin-mediated endocytosis (Day, 2003, Bousarghin, 2003, Smith, 2007, Hindmarsh, 2007). Although a few contradictory studies suggest that HPV16 is clathrin and caveolaen independent (Spoden, 2008). The virus then uncoats and delivers its genome of 8 genes to the host cell nucleus to be expressed as autonocmous replicating episoma or extrachromasomal replication. These eight genes are named for when they are expressed during the virus’s occupation of its host: early (E) and late (L). E1,2,4 and 5 are important to genome replication, E6 and E7 are oncogenes and when unchecked can cause cancerous growth of host cell. E6 is thought to complex with p53 (Werness, 1990) which promotes the degradation of p53 via the ubiquitin pathway (Schffner et al., 1990). This degradation of p53 contributes to the oncogenic potential of high-risk HPVs. Because tt has also been shown that E6 can bind with p53 without degradation (Crook et al., 1991), it was thought that blocking E6-mediated degradation of p53 might be sufficient to reactivate p53 function. However, blocking E6-induced degradation showed that additional DNA damaging

Sexually transmitted diseases are caused by a wide range of viruses. The most common viruses are: HIV-1, HSV-1/2, and HPV. Often the contraction of these viruses goes undiagnosed until the patient has acquired severe symptoms, by this time they have also transferred the disease to another individual. For this reason, the importance of developing and understanding immunotherapeutic strategies has become essential for immunologists (5). There are many factors that contribute to viral infection, therefore, targeting these virus specific factors is a key to preventing viral spread to neighboring cells. Factors like viral attachment, entry, un-coating, synthesis, assembly, and

Rationale: HPVs initially bind to negatively charged cell-surface glycosaminoglycans, particularly heparin sulfate proteoglycans, on cultured epithelial cells (63-65). In mammals, both spermatozoa and oocytes surface proteins are highly glycosylated, and these glycoproteins may attract papillomavirus (66). Whether these bindings are reversible is unknown. Semen washing procedures showed effective for blocking the HIV transmission (20), but they do not eliminate HPV infection from spermatozoa in infertile patients (21). For humans, the semen and spermatozoa have been reported positive for HPV (16-19, 49, 50, 67). Direct binding of

Human Papillomavirus (HPV) is DNA virus of the papillomavirus family, and it is identified has one of the most common causes of sexually transmitted infections (STI) in the world (Stanley, 2008). It is important to note that there are more than

Wounding has been reported necessary for a HPV pseudovirus to deliver marker gene in mouse vaginal tract (Roberts et al., 2007). For skin infection, we found that pre-wounding did improve the viral infectivity in our rabbit papillomavirus model (Cladel et al., 2008). We compared vaginal infection with and without wounding in our MmuPV1 model. Although we found that wounding promoted infection at an earlier time, but it is not essential for MmuPV1 infection at the genital tract. One reason is the nature of low amount of target DNA encapsidating inside pseudovirus (Holmgren et al., 2005). Our unpublished study demonstrated that natural virions contain most viral DNA. Therefore, the efficiency of naturally viral infection is much higher when compared with the

It represents 2.5% of all oral lesions and is the most frequently observed papillary lesion in the oral cavity (2). The majority of these lesions are associated with varying HPV subtypes and considerable research has been conducted to identify them. It should be noted that not all squamous papillomas have a viral etiology; however, this discussion will focus on those that do. Epidemiologically, HPV is a significant health burden worldwide as well as to the U.S population. Currently, the U.S estimated incidence of genital HPV is 5.5 million, and the prevalence of current infection is estimated at 20 million (3). Assessment of HPV infection is accomplished by HPV DNA detection tests through PCR technique. Data on infection in women is more numerous, due to the availability of standardized methods of mucosal sampling. Detection is essential in infected patients as the majority of cases can appear asymptomatic, (especially in men) with no means of detection physically or cytologically. HPV is a double stranded DNA virus of the papovavirus family containing a single molecule (2). The various subtypes are antigenically distinct yet still retain common antigenic determinants. Proliferation of the virus is dependent on the host cell’s DNA and occurs in the nuclei of the host’s epithelial cells. Expression of the viral genome comes about due to the host DNA

Any threats that can be resolved by a healthy individual might become problematic for these patients. The blood safety becomes a major concern to protect them from catching diseases from the blood products. In our preliminary studies, we have demonstrated that intravenous infections via ear vein with papillomavirus induced tumor growth at locally wounded skin, anogenital, and oral mucosal sites in these two preclinical models. Transfusion with virus contaminated blood also induced tumors at locally wounded sites. To further delineate the risk of blood born papillomavirus and the viral DNA, we plan to determine the threshold dose with a serial of virus and viral DNA dilutions. Both immunocompetent and compromised animals of different ages will be tested in the current study to determine whether different threshold doses for infection by the circulating virus exist. Viral presence will be tracked with our established virological assays. Serum samples will be collected to monitor antibody generation.