Immune Evasion by Persistent Viruses and Cancers: Blocking Evasion as a Rational Design to Treat Viral Infections and Cancers

Abstract

Vaccines are the most cost-effective and successful preventative measure against infectious diseases. Childhood vaccinations had a tremendous impact on public health. The mortality and morbidity associated with diseases such as polio, smallpox, measles, mumps, rubella, diphtheria, pertussis, tetanus, have reduced radically (> 90100%) due to prophylactic vaccines provided during childhood. The success of these preventive vaccines lies in their ability to induce an effective B cell memory and ongoing production of antibodies that either directly neutralize pathogens, or operate with complement system or other immune cells to kill pathogens. CD8 + T cell responses are also a key component of protective immunity, particularly in case of virus infections. More recently, development of cancer vaccines is breaking new grounds. Ability to evade host immune system is a major roadblock in achieving complete protection against persistent viral infections and malignant diseases. DNA viruses such as herpes viruses and poxviruses encode several genes that directly evade the host innate and adaptive immune responses [1-2]. Because of potent immune evasion mechanisms, and ability of virus to persist in immune competent hosts, a vast majority of the global population remain infected with at least one of the herpes virus. Herpes Simplex virus (HSV) type 1 and 2, Varicella Zoster Virus (VZV), Human Cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and are few examples of herpes viruses [3]. Poxviruses cause acute infections, and may establish persistent infection based on the immunocompetence of the host and route of infection [4]. Vaccinia virus is a poxvirus family virus, which was used as a successful vaccine to eradicate the human pathogen variola virus (smallpox). Human papilloma virus (HPV) is a causative agent for cervical cancer, and establishes persistent infection. Recombinant protein subunits vaccine is currently used to combat cervical cancer successfully. RNA viruses like human immunodeficiency virus (HIV) and hepatitis C virus (HCV) undergo extensive antigenic variations due to selective pressure of the immune system, which lead to immune escapes [5,6]. In a computational model of HIV-1 infection dynamics in lymphoid tissue demonstrated that evasion of immune surveillance by persistent virus is sufficient to cause treatment failure in case of structured interruption highly active antiretroviral therapy (HAART) [7].