Ebola virus as a sexually transmitted infection

BACKGROUND Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone. METHODS We enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD. RESULTS Of 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP. CONCLUSIONS These data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.)

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“…The potential for the persistence of EBOV, particularly in the semen of male survivors, arouses concern about the risk of sexual transmission. 6 …”

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confidence: 99%

Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors — Final Report

Deen¹,

et al. 2017

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“…Identification of inhibitors that block such interactions may be useful for a wide array of PPxY-containing viruses that hijack or recruit WW domaincontaining E3 ligases during the late step of budding. Such inhibitors may be particularly useful for the treatment of Ebola virus disease, as EBOV was shown recently to cross the bloodbrain barrier and re-emerge months later in the central nervous system and eye, as well as in other immunologically privileged sites that are inaccessible to antibody therapy (152)(153)(154)(155)(156)(157)(158)(159)(160)(161)(162)(163)(164)(165).…”

Section: Filoviruses and Other Ppxy-containing Virusesmentioning

confidence: 99%

Viruses go modular

Shepley-McTaggart

Fan

Sudol

et al. 2020

Journal of Biological Chemistry

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The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain-containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus life cycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW-domain interactions that could be used as antiviral therapeutics. . 2 The abbreviations used are: PPxY, proline-proline-x-tyrosine motif; AdV, adenovirus; ART protein, arrestin-related trafficking protein; BAG3, BCL2associated athanogene 3; BUL1 and -2, binds ubiquitin ligase proteins 1 and 2; CASA, chaperone-assisted selective autophagy; CIRF, cell-intrinsic restriction factor; EBV, Epstein-Barr virus; EBOV, Ebola virus; ESCRT, endosomal sorting complex required for transport; HECT, homologous to the E6AP carboxyl terminus (E3 ligase family); HHV, human herpes virus; HTLV-1, human T-cell leukemia virus 1; IFITM3, interferon-induced transmembrane protein 3; ISG15, interferon stimulated gene 15; ITCH (AIP4), Itchy E3 ubiquitin protein ligase; LDI-1 and -2, late domain-interacting proteins 1 and 2; L domain, viral late domain; LMP2A, latent membrane protein 2A; MARV, Marburg virus; MLV, murine leukemia virus; Nedd4, neuronal precursor cell-expressed developmentally down-regulated 4; PVI, preprotein VI (membrane lytic internal capsid protein); Rsp5, yeast reverses SPTphenotype protein 5 (E3 ubiquitin-protein ligase); RSV, Rous sarcoma virus; SMURF1 and -2, Smad ubiquitin-regulating factors 1 and 2; TBSV, tomato bushy stunt virus; Tsg101, tumor susceptibility gene 101; VLP, virus-like particle; VSV, vesicular stomatitis virus; WOX1, WW domain-containing oxidoreductase; WWP1 and -2, WW domain-containing E3 ubiquitin protein ligase 1 and 2; MS, multiple sclerosis. cro REVIEWS 4604

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“…7 8 Survivors infected with HIV might also maintain Ebola virus in sanctuary sites, such as semen, for longer than currently described. 9 Information is needed on dual infection with HIV and Ebola, and interventional studies and reports on outcomes from Ebola treatment centres in west Africa should consider this potential confounder.…”

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confidence: 99%