Fanconi Anemia Patients Are More Susceptible to Infection with Tumor Virus SV40

Abstract

Fanconi anemia (FA) is a recessive DNA repair disease characterized by a high predisposition to developing neoplasms. DNA tumor polyomavirus simian virus 40 (SV40) transforms FA fibroblasts at high efficiency suggesting that FA patients could be highly susceptible to SV40 infection. To test this hypothesis, the large tumor (LT) antigen of SV40, BKV, JCV and Merkel Cell (MC) polyomaviruses were tested in blood samples from 89 FA patients and from 82 of their parents. Two control groups consisting of 47 no-FA patients affected by other genetic bone marrow failure diseases and 91 healthy subjects were also evaluated. Although JCV, BKV and MC were not found in any of the FA samples, the prevalence and viral load of SV40 were higher in FA patients (25%; mean viral load: 1.1×102 copies/105cells) as compared with healthy individuals (4.3%; mean viral load: 0.8×101 copies/105cells) and genetic controls (0%) (p<0.005). A marked age-dependent frequency of SV40 was found in FA with respect to healthy subjects suggesting that, although acquired early in life, the virus can widespread more easily in specific groups of population. From the analysis of family pedigrees, 60% of the parents of SV40-positive probands were positive for the virus compared to 2% of the parents of the SV40-negative probands (p<0.005). It is worthy of note that the relative frequency of SV40-positive relatives detected in this study was the highest ever reported, showing that asymptomatic FA carriers are also more susceptible to SV40. In conclusion, we favor the hypothesis that SV40 spread could be facilitated by individuals who are genetically more susceptible to infection, such as FA patients. The increased susceptibility to SV40 infection seems to be associated with a specific defect of the immune system which supports a potential interplay of SV40 with an underlying genetic alteration that increases the risk of malignancies.

Fanconi Anemia Proteins Function in Mitophagy and Immunity

“…A role for FANCC in virophagy may mechanistically explain either the increased prevalence of certain viral infections (such as human papilloma virus [HPV] or SV40) in FA patients (Comar et al, 2013; Sauter et al, 2015) or the role of FA pathway components (such as FANCA and FANCD2) in restricting the HPV life cycle (Hoskins et al, 2012). Furthermore, the failure to remove aggregates of viral proteins in the setting of Fancc deficiency may represent an environmental trigger that functions in the pathophysiology of FA (Parmar et al, 2009).…”

Neutralizing and IgG Antibodies against Simian Virus 40 in Healthy Pregnant Women in Italy

“…However, the International Agency for Research on Cancer decided recently that there was not enough firm evidence to classify SV40 as a carcinogenic viral agent of humans [40] . Although there is strong evidence that infections have occurred in certain populations in different geographic regions, more studies are needed of the current prevalence of SV40 infections in humans and the natural history of those infections [3] , [4] , [39] , [41] , [42] .…”

Detection of human papillomavirus in the oral cavities of persons with Fanconi anemia

“…We also explored correlates of oral HPV infection. Understanding the epidemiology of oral HPV infections in persons with FA may help determine whether their increased risk of HNSCC is partially due to either increased susceptibility to HPV infection [potentially due to impaired immune function (Myers et al , ; Comar et al , )], or to differences in the natural history of HPV infection that accelerate carcinogenic progression. In addition, characterizing type‐specific HPV prevalence in persons with FA may help determine the potential benefit of prophylactic HPV vaccination to prevent HPV‐positive HNSCC.…”