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Background:  Spuma retroviruses, or foamy viruses (FV), have been described as “between retroviruses and hepadnaviruses,” yet the closely related viruses in those families are pathogenic, while FV are not. Virus–host interactions that lead to nonpathogenic outcomes have become a focus of interest since it is thought that pathogenic viruses originated from nonpathogenic viruses that had crossed species. FV establish lifelong, apathogenic persistence in vivo yet are extremely cytopathic to many cell types in vitro. FV are thought to have limited replication within their hosts, viral DNA being widely disseminated, but viral RNA only sporadically detectable in the oral mucosa.

Methods:  We addressed this paradigm by measuring FV DNA and RNA in tissues and buccal swabs taken from naturally FV-infected rhesus macaques. Using quantitative RT-PCR, we discovered that FV replication was not as sporadic as previously thought, and was evident in tissues outside of the oral mucosa, including the lung and lymph nodes. Viral RNA was detected in buccal swabs taken from all of the FV seropositive rhesus macaques tested, with loads ranging from 1.3 x 10² to 1.6 x10⁶ copies per 10⁴ cell equivalents. Examination of diverse tissues revealed FV RNA in the pharyngeal and buccal epithelium, tongue, tonsil, lung, and mesenteric lymph nodes, but not in the parotid or submaxillary salivary glands, CNS tissues, bladder, colon, or small intestine. However, there was altered tissue distribution of FV RNA in SIV-immunosuppressed hosts. Specifically, FV RNA was detectable in the small intestine of all of the SIV-immunosuppressed rhesus macaques tested, ranging from 8.2 x10³ to 6.3 x10⁴ copies per 10⁴ cell equivalents, but not in any of the immunocompetent rhesus macaques. Other persistent viruses such as HIV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) are controlled by host immune mechanisms, as evidenced by increased viral replication with host immunosuppression.

Conclusions:  Taken together, we suggest that that FV replication is more consistent and widespread than previously thought, and that the host immune system may play a role in controlling FV replication in the small intestine.

Keywords: foamy virus; latency; immune control