Cashion M F, Banks W A, Bost K L, Kastin A J
Veterans Affairs Medical Center, New Orleans, LA, USA.
Brain Res. 1999 Mar 20;822(1-2):26-33. doi: 10.1016/s0006-8993(99)01069-0.
The blood-brain barrier (BBB) restricts the entry of antiviral agents into the CNS thereby facilitating the creation of a reservoir of HIV that could potentially reinfect peripheral tissues. We characterized the efflux from brain of radioactively labeled viral coat HIV-1 gp120 (I-gp120) after intracerebroventricular (i.c.v.) injection. The half-time disappearance rate of I-gp120 from brain was 12.6 min, which was faster than could be explained by the reabsorption of cerebrospinal fluid into blood but could not be explained by a saturable transporter. After i.c.v. injection, I-gp120 appeared in the serum and was sequestered by spleen and the cervical nodes, demonstrating a potential for virus within the CNS to reinfect peripheral tissues. However, the amount of I-gp120 appearing in serum was less than that expected based on the efflux rate, whereas uptake by the cervical nodes was much greater after i. c.v. than after i.v. injection of I-gp120. These findings were explained by drainage from the brain directly to the cervical lymph nodes through the brain's primitive lymphatic system. These lymphatics potentially provide a pathway through which CNS reservoirs of HIV-1 could directly reinfect lymphoid tissue without being exposed to circulating antiviral agents.
血脑屏障（BBB）限制抗病毒药物进入中枢神经系统（CNS），从而促使形成一个HIV储存库，该储存库有可能重新感染外周组织。我们对脑室内（i.c.v.）注射放射性标记的病毒外壳HIV-1 gp120（I-gp120）后其从脑内的流出情况进行了表征。I-gp120从脑内消失的半衰期为12.6分钟，这比脑脊液重吸收进入血液所能解释的速度要快，但无法用可饱和转运体来解释。脑室内注射后，I-gp120出现在血清中，并被脾脏和颈淋巴结截留，这表明中枢神经系统内的病毒有重新感染外周组织的可能性。然而，血清中出现的I-gp120量低于基于流出速率所预期的量，而颈淋巴结的摄取在脑室内注射I-gp120后比静脉注射后要大得多。这些发现可以通过脑内的原始淋巴系统直接引流至颈淋巴结来解释。这些淋巴管可能提供了一条途径，通过该途径，HIV-1的中枢神经系统储存库可以直接重新感染淋巴组织，而无需接触循环中的抗病毒药物。
