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Rabies virus: route of dissemination.

Posted by ricardo_mendes on 07 Feb 2010 at 11:07 GMT

The mean survival time after SB i.v. infection (10.4±2.4 days) was not significantly different from the survival time after SB i.m. infection (p>0.05, Figure 1B).

I read with interest the article by Preuss et al. (2009) suggesting that hematogenous spread of SB can lead to fatal encephalopathy through direct retrograde invasion of the CNS at the neurovascular interface of the hypothalamus-hypophysis system.
The authors try to obtain evidence that the rabies virus might have the capacity to reach the brain from a peripheral site via hematogenous spread. They infected Swiss Webster mice with focus forming units of SB or DOG4 rabies virus strain into the heat-dilated tail vein and into the right gastrocnemius muscle.
All mice infected with the SB strain develop rabies symptoms like fur ruffling, weight loss and hunchback posture. The authors revealed that the mean survival time after SB i.v. infection was not significantly different from the survival time after SB i.m. infection (p<0.05). And, that the weight loss in these two SB groups was practically identical, referring to the percentage of loss, but also in regard to the time in days when this loss occurs.
During the incubation period, the rabies virus propagates in the muscle cells around the port of entry and invades the peripheral nervous system. It then migrates centrally to the central nervous system, following the flow within the axoplasm of peripheral nerves at a velocity varying from 20 to 400 mm per day [1-3].
About the methodology used by the authors, it can not be guaranteed that in the i.m injection, the virus did not invade the vasculature and reach the CNS by a hematogenous route, detrimental to the comparison with groups. Although, if the two injected via were correctly respected by the virus, the time necessary for the virus to reach the CNS, using the axonal transport, should be larger than in the i.v. injection, with a significant difference in the survival time and development of clinical signs. Especially, taking in to account that the authors report the port of entry of the i.v. SB infection was the neurovascular interface of the hypothalamus-hypophysis system, a structure close to the CNS.
On the other hand, as they detect higher levels of viral burden by qRT-PCR in spinal cord (p<0.05) and brain, only 2 hours after infection in the SB i.v., comparing with the SB i.m., it should be expected a faster appearance of clinical signs in the first group, consequently, significant differences respect this parameter.
Also, it would be of interested, explain the infection doses used, since authors referred in separated parts of the text, different focus forming units injections: 106, 107 and 5x106.

1. Aquino DA, Bisby MA, Ledeen WW (1987) Bidirectional transport of gangliosides, glycoproteins and neutral glycosphingolipids in the sensory neurons of rat sciatic nerve. Neuroscience 20: 1023-1029.

2. Fishbein DB, Robinson LE (1993) Rabies. N Engl J Med 329:1632-8

3. Klingen Y, Conzelmann KK, Finke S (2008) Double-Labeled Rabies Virus: Live Tracking of Enveloped Virus Transport.. J Virol 82: 237–245.

No competing interests declared.