Fachbereich Veterinärmedizin



    Diversität und Evolution von Adenoviren bei Primaten in Subsahara-Afrika (2016)

    Hoppe, Eileen (WE 5)
    Berlin: Mensch und Buch Verlag, 2016 — VI, 103 Seiten
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000103599
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
    +49 30 838 51833

    Abstract / Zusammenfassung

    Human adenoviruses (HAdV A-G) are highly prevalent in the human and nonhuman primate (NHP) population. HAdV-B is an important human pathogen causing respiratory tract-, eyeand urinary tract infections and also was detected in feces of great apes in large quantity. The origin and evolution of HAdV-B has so far not been studied in detail. The goals of the present study were to study the molecular epidemiology of HAdV infecting great apes and humans in tropical Africa with focus on HAdV-B, to investigate the crossspecies transmission frequency of HAdV-B and to explore HAdV-B recombination in wild great apes. 568 fecal samples were collected in the wild from eight great ape species and subspecies of nine forest sites throughout sub-Saharan Africa. In addition, 292 samples from people living in neighboring villages at four of these sites were tested. All samples were analyzed with generic and specific PCR systems. High prevalence of HAdVs was detected in all hosts. Cumulative primate AdV prevalence was 51% (75/146) in chimpanzees, 94% (79/84) in bonobos, 74% (251/338) in gorillas, and 69% (201/292) in humans. While we identified HAdV-C in all investigated species, HAdV-D was detected only in humans and HAdV-E in chimpanzees and bonobos. HAdV-B was found in 55% of all investigated gorilla samples and in some chimpanzee samples. Humans and bonobos were HAdV-B negative. To examine the evolutionary relationships of great ape and human members of HAdV-species, additional sequence information was created by long-distance PCR amplifying a block of 4 genes (V, pX, pVI, hexon). First the genetic diversity comprised in this dataset was explored by performing a ML analysis using PhyML. A high HAdV-B diversity was found in gorillas. In a next step, gorillas were identified as the best supported ancestral host of the entire HAdV-B group performing a Bayesian framework followed by assumption that transmissions from gorillas to humans and chimpanzees must have occur. By quantifying these transmission events, the most frequent host switches were those from gorillas to chimpanzees with 6 to 7 transmissions. Two HAdV-B transmission events from gorillas to humans were identified. With a Bayesian chronogram transmissions were located in time. The inferred rate of gorilladerived HAdV-B transmission events was low, with a mean of 2.2 transitions to chimpanzees per My and 0.7 transitions to humans per My. Interestingly, some transmission events occurred before our species emerged. This indicated that HAdV-B affected human health for the entire lifetime of our species. To identify recombinants of HAdV-B from wild gorillas larger genome fragments and a near complete genome were determined and in mVISTA analysis pairwise aligned. While the central part of the wild gorilla´s HAdV-B genome was most similar to a captive gorilla´s HAdV-B genome (SAdV-28.2) the outer portions were most closely related to a captive´s chimpanzee HAdV-B genome (SAdV-33). In addition, a comparative phylogenomic approach was performed analyzing general hot spots (penton base to hexon gene; fiber gene) of AdV recombination. The phylogenetic trees revealed discordance in HAdV-B tree shape and subclade composition indicating that genome-wide ecombination occurred during evolution of wild gorilla’s members of species HAdV-B. It was concluded that AdV recombination occurs also in natural habitats and not only in sites of artificially close inter-primate contact like zoological gardens. The generated data show that current-day transmissions of HAdV-B members from great apes to humans with subsequent emergence of recombinants cannot be excluded. The likelihood for infection with such recombinant AdVs increases for people in some regions of sub-Saharan Africa, because of the high AdV prevalence in NHP, overlapping habitats of humans and great apes and bush meat hunting and trade. Based on the data presented here it can be concluded that HAdV-B circulating in humans are of zoonotic origin. With regard to the importance of zoonoses for public health further investigations on primate AdVs in sub-Saharan disease outbreaks are needed.