Virulence of Avian Influenza A Viruses for Squirrel Monkeys

Abstract

Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus, A/Udorn/307/72 (H3N2). In squirrel monkeys, the 10 avian influenza A viruses exhibited a spectrum of replication and virulence. The levels of virus replication and clinical response were closely correlated. Two viruses, A/Mallard/NY/6874/78 (H3N2) and A/Pintail/Alb/121/79 (H7N8), resembled the human virus in their level and duration of replication and in their virulence. At the other end of the spectrum, five avian viruses were restricted by 100- to 10,000-fold in replication in the upper and lower respiratory tract and were clearly attenuated compared with the human influenza virus. In hamsters, the 10 viruses exhibited a spectrum of replication in the nasal turbinates, ranging from viruses that replicated as efficiently as the human virus to those that were 8,000- fold restricted. Since several avian viruses were closely related serologically to human influenza viruses, studies were done to confirm the avian nature of these isolates. Each of the avian viruses plaqued efficiently at 42°C, a restrictive temperature for replication of human influenza A viruses. Avian strains that had replicated either very efficiently or very poorly in squirrel monkeys still grew to high titer in the intestinal tracts of ducks, a tropism characteristic of avian, but not mammalian, influenza viruses. These observations indicate that some avian influenza A viruses grow well and cause disease in a primate host, whereas other avian viruses are very restricted in this host. These findings also provide a basis for determining the gene or genes involved in the restriction of replication that is observed with the attenuated avian viruses. Application of such information may allow the preparation of reassortant viruses derived from a virulent human influenza virus and an attenuated avian virus for possible use in a live attenuated vaccine for prevention of influenza in humans.

Evaluation of the Biological Properties and Cross-Reactive Antibody Response to H10 Influenza Viruses in Ferrets

“…In human trials, volunteers were intranasally inoculated with 10 6 EID 50 of A/turkey/Minnesota/3/1979 (H10N7). Viral shedding was detected in 6 of 15 volunteers (titers not reported) and mild clinical disease in 8 of 15 volunteers (38). The reports of mild illness and viral shedding with variable peak titers are consistent with our observations in ferrets.…”

“…These isolates were tk/MN/79, A/teal/Egypt/12908-NAMRU3/2005 (H10N1), and A/harbor seal/Germany/ PV20762_TS/2014 (H10N7) (32,37,38). In studies with tk/MN/79, ferrets shed virus for 7 days, with a peak titer of 10 7.3 50% egg infective doses (EID 50 )/ml following intranasal inoculation (38). Our findings are consistent with this report, as we observed titers of tk/MN/79 in nasal turbinates between 10 6 and 10 8 TCID 50 /g (Fig.…”

Avian Influenza Virus (H5N1): a Threat to Human Health

“…Avian influenza viruses do not efficiently infect humans or nonhuman primates (7,152). Conversely, human viruses do not efficiently replicate in ducks (78).…”

Replication of SARS coronavirus administered into the respiratory tract of African Green, rhesus and cynomolgus monkeys

“…In addition to the importance of establishing the microbial etiology of a disease, animal models are critical to the study of disease pathogenesis and the evaluation of treatment and control strategies. Non-human primates have been useful in evaluating vaccines and studying disease pathogenesis for several respiratory viruses including influenza, respiratory syncytial virus, and human parainfluenza viruses (Crowe et al, 1993;Durbin et al, 2000;Murphy et al, 1982;Rimmelzwaan et al, 2001;Skiadopoulos et al, 2002). These studies demonstrated that the susceptibility of different monkey species to specific respiratory viruses is variable.…”